Does 'Dementia Gene' Double Risk of Severe COVID-19?

Nicky Broyd

May 26, 2020

UK/US observational research finds having a faulty gene linked to dementia doubles the risk of a person developing severe COVID-19 even if they haven't developed dementia.

University of Exeter Medical School and the University of Connecticut School of Medicine researchers used UK Biobank data to reach their findings about the APOE gene (e4e4). The study has been published in the Journal of Gerontology: Medical Sciences.

Earlier this month NHS England data put dementia in second place (18%) after diabetes (26%) in the list of COVID-19 comorbidities.

Faulty Gene

Two faulty copies of this gene are found in 1 in 36 people of European descent. This has previously been linked to an almost 15 times increased risk of Alzheimer's disease in Caucasian people.

In the analysis, 2.36% (n=9,022) of participants with European ancestries (n=382,188) had the APOE e4e4 faulty gene, but 5.13% (n=37) of those who tested positive for COVID-19 (n=721) had this gene variant.

The team said this suggests the risk is doubled compared to the more common form of the APOE gene e3e3 (410 per 100,000 versus 179 per 100,000).

David Melzer, professor of epidemiology and public health at Exeter, who led the team, said in a news release: "Several studies have now shown that people with dementia are at high risk of developing severe COVID-19. This study suggests that this high risk may not simply be due to the effects of dementia, advancing age or frailty, or exposure to the virus in care homes."

He says: "The effect could be partly due to this underlying genetic change, which puts them at risk for both COVID-19 and dementia.”

Dementia is not one of the UK's 'home shielded' conditions but people with dementia make up 50.1% of care home residents and 66.2% of care/nursing home residents.

Small Numbers 

Responding to the findings in a statement, Dr Carol Routledge, director of research at Alzheimer’s Research UK, said: "We don’t yet know how this Alzheimer's risk gene might make people more susceptible to the virus. Despite the large study group, only 37 people with the risk gene tested positive for COVID-19, and we must be careful about the conclusions we draw from such small numbers."

She added: "This study analysed data from participants with European ancestry so the findings may not be relevant to other groups and it is important for other studies to look into COVID-19 risk for people with a different genetic background."

Other experts commented via the Science Media Centre.

Professor Tara Spires-Jones, UK Dementia Research Institute group leader and deputy director, Centre for Discovery Brain Sciences, The University of Edinburgh, said: "An important limitation of the current paper is that this type of observational study cannot prove that the APOE4 gene is the cause of the observed increased risk of COVID-19. The scientists did a thorough job of trying to control for other things associated with APOE4 that could account for the risk, but it is still possible that there is an unknown related factor causing the increased risk."

Prof David Curtis, honorary professor, UCL Genetics Institute, said: "The concern I have about this study is that the results could potentially be explained by the possibility that more subjects with two copies of the high risk APOE e4 allele might have had dementia than those who had none."

He added: "I'm afraid this study does not really convince me that the APOE e4 allele is really an independent risk factor for severe COVID-19 infection."

APOE E4 genotype predicts severe COVID-19 in the UK Biobank community cohort’ by Chia-Ling Kuo published in the Journal of Gerontology: Medical Sciences 


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