In a recent study published in the Journal of Alzheimer’s Disease, researchers in the United States investigated whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections could trigger the development of new-onset Alzheimer’s disease (AD)
It has been suggested that infections may lead to AD development; however, it is not clear whether SARS-CoV-2 infections can increase the risk for AD. The enhanced risk for SARS-CoV-2 infections among AD patients and the long-term neurologic sequela of coronavirus disease 2019 (COVID-19) (partly representing inflammation-associated changes, which are critical in AD neurological pathophysiology) are indicative of a two-way relationship between SARS-CoV-2 infections and AD. The study’s authors previously showed a high risk of breakthrough SARS-CoV-2 infections among fully vaccinated AD patients.
Study: Association of COVID-19 with New-Onset Alzheimer’s Disease. Image Credit: Donkeyworx / Shutterstock
About the study
Researchers examined the risk of new-onset AD among SARS-CoV-2-positive patients in the present retrospective cohort study.
The study comprised 6,245,282 adults aged ≥ 65 with no prior AD diagnosis. Data were obtained from de-identified EHRs (electronic health records) of more than 95 million SARS-CoV-2-positive patients of outpatient and inpatient visits from healthcare organizations (n=68) across 50 states of the United States (US) covering different geographical, race, age, insurance, and income groups.
The study participants were classified into two groups: (i) the SARS-CoV-2-positive group comprising 410,748 individuals who acquired SARS-CoV-2 infections between 2 February 2020 and 30 May 2021; (ii) the SARS-CoV-2-negative group comprising 5,834,534 individuals with no SARS-CoV-2 exposure but had sought medical care from healthcare organizations between 2 February 2020 and 30 May 2021 for non-COVID-19 reasons.
AD and SARS-CoV-2 infection status were based on the ICD-10 (international classification of diseases) codes and laboratory-based analyses. The risk of new-onset AD was examined for the two groups stratified by race (Hispanics, Whites, and Blacks, Whites) and age (65 to 74 years, 75 to 84 years, and ≥85 years).
Propensity score matching (PSM) was performed in a 1:1 ratio for demographical parameters and adverse socioeconomic health determinants such as educational difficulties, occupational exposures, social, physical, or psychosocial environments, and factors known to increase AD risk. The team used the Kaplan-Meier estimator and Cox’s proportional modeling to analyze and calculate hazard ratios (HRs).
Results
After PSM, the data showed that the average age of individuals in both study groups was 74 years, most of whom were females (54%). The average proportions of Blacks, Whites, and Hispanics were 10%, 75%, and 6.7%, respectively, and adverse socioeconomic and psychosocial circumstances were reported for 13% of the sample population.
Comorbid conditions such as hypertension, obesity, type II diabetes, depression, hearing loss, traumatic brain injury, tobacco smoking, and heavy alcohol consumption were prevalent among 60%, 23%, 30%, 22%, 5.8%, 3.1%,11%, and 3.8% of the sample population, respectively.
Prior to PSM, the risks of new-onset AD among SARS-CoV-2-positive and SARS-CoV-2-negative individuals were 0.7% and 0.4%, respectively. Post PSM, the risk increased among SARS-CoV-2-positive individuals compared to SARS-CoV-2-negative individuals (HR: 1.7).
HR values for the risk of new-onset AD among COVID-19 patients aged 65 to 74 years, 75 to 84 years, and ≥85 years were 1.7, 1.6, and 1.7, respectively. HR values for the risk among females (HR 1.8) were greater than those for males (HR 1.5). HR values for the risk among Blacks, Whites, and Hispanics were 1.6, 1.6, and 1.3, respectively. Taken together, the risk was highest among adults aged ≥ 85 years (HR 1.9) and among females (HR: 1.8).
Overall, the study findings showed that SARS-CoV-2-positive female adults aged ≥ 85 years were at a significantly higher risk for new-onset AD within 360 days of SARS-CoV-2 infection diagnosis. However, future studies are required with data validation from multiple sources and longer follow-up periods to elucidate the mechanisms of and for continued surveillance of the impact of SARS-CoV-2 infections on AD.
Study limitations
The limitations of the present study include the retrospective and observational nature of the study that could introduce potential biases and AD diagnosis inaccuracy, which may not have affected the relative risk analyses considerably since both groups were formed from the same dataset.
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