Alzheimer disease, dementia and related cognitive disorders are the most significant risk factors for COVID-19, researchers found in an observational cohort study published in Brain, Behavior, and Immunity.

The researchers tested the association of COVID-19 status with 974 medical conditions and 30 blood biomarkers by using medical records from 389,620 study participants of European descent from the UK Biobank, a population-based prospective study that recruited more than 500,000 individuals aged 40 to 69 between 2006 and 2010.

Individuals who enrolled outside of England, died before September 2019, or had a self-reported sex not consistent with genetic information were not included. The researchers included COVID-19 laboratory test results dated between March 16 and May 18, 2020 that were associated with any of the remaining 389,620 patients.

The researchers analyzed the inpatient hospital records, cancer registry, and death registry in the database, identified cases of hospitalization and testing for COVID-19, collected the 30 biomarkers from the UK Biobank cohort’s blood samples. They found that 1,091 of the 3,884 patients who tested for COVID-19 had tested positive at least once while in the hospital.

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The researchers found an association between COVID-19 and delirium, dementia, amnestic and other cognitive disorders (P =1.36×10-44, odds ratio [OR], 1.90; 95% confidence interval [CI], 1.24–2.90 in combined samples; OR, 2.06; 95% CI, 1.11–3.81 in males), dementia (P =3.48×10-44; OR, 2.16; 95% CI, 1.36–3.42 in combined samples; OR, 2.05; 95% CI, 1.05–3.98 in males; OR, 2.24; 95% CI, 1.18–4.24 in females), and Alzheimer disease (P =2.45×10-27; OR, 2.29; 95% CI, 1.25–4.16 in combined samples; OR, 2.40; 95% CI, 1.02–5.62 in males). Of the 992 patients with dementia in the cohort, 45 tested negative and 34 tested positive for COVID-19. Of the 509 patients with Alzheimer disease in the cohort, 25 tested negative and 20 tested positive for the coronavirus.

The patients who tested positive for COVID-19 also tended to be older (P =.024), more frequently male (P =7.33×10-8), have a higher body mass index (BMI) (P =7.27×10-18) and more frequently have a history of smoking (P =2.84×10-5) compared to the rest of the cohort, and they had higher BMI (P =3.9×10-3) and more tendency to be male (P =3.2×10-3) than those who tested negative for COVID-19.

Limitations of the study included susceptibility to collider bias due to the small sample size, the inability to provide additional information about specific symptoms or outcomes of the subjects with COVID-19 and the inability to address the causal roles of risk factors.

“Based on our findings, cognitive disorders are likely risk comorbidities in older groups and their associated susceptibility to severe COVID-19 is not merely a result of an older age,” the researchers said. “Another possible explanation for the finding that more individuals with mental disorders suffer from COVID-19 is that they are at a higher risk of viral infection because of their limited self-care ability and their frequent interactions with care providers. Overall, these results should help stimulate COVID-19 research on the special needs of patients with these cognitive conditions. Given the different risks faced by the elderly living with different styles, a more comprehensive strategy with precise approaches of primary prevention may be desirable during this and similar pandemics.”

“Our findings identified associations of an extensive range of pre-existing conditions and genetic variants as being associated with COVID-19,” the researchers said. “However, the real causal effects of risk factors on COVID-19 susceptibility are likely to vary by genetic background, lifestyle, and social connectedness and are presumably more complicated than indicated by our population-level screen.”


Zhou J, Liu C, Sun Y, Huang W, Ye K. Cognitive disorders associated with hospitalization of COVID-19: Results from an observational cohort study [published online October 24, 2020]. Brain, Behav, Immun. doi: 10.1016/j.bbi.2020.10.019