Having a faulty gene linked to dementia may double the risk of becoming severely-ill with the coronavirus, a study has claimed.
Experts found carriers of the APOE e4 gene were more likely to have a severe case of Covid-19, than those with a more common variant.
The same faulty gene is already known to increase the risk of developing Alzheimer’s disease in old age by up to 14-fold.
Scientists studied the DNA of almost 40,000 Britons aged between 48 and 60 years old to make the link.
Almost one in five people who have died with COVID-19 in the UK also had dementia, the most common form of Alzheimer’s.
One explanation for people with dementia being more vulnerable to COVID-19 could be because the virus spread rapidly in care homes.
But the research, published in the Journal of Gerontology: Medical Sciences, could help to explain the high death rates being seen in people with dementia.
Having a faulty gene linked to dementia doubles the risk of severe Covid-19, a study has found
Almost one fifth of COVID-19 victims in hospitals had dementia, according to official figures from NHS England
The study was a joint endeavour by a team of academics at the University of Exeter Medical School and the University of Connecticut.
It used data from the UK Biobank – a study of 500,000 volunteers set up in 2006 for researchers to track the health of participants over time.
Experts analysed only 382,188 participants who had European ancestries, therefore their findings can only be applied to that group, with an average age of 68.
They looked at a gene called APOE, of which there are three variants. In this analysis, 69 per cent had two copies of the e3 variant, the most common genotype.
Some 28 per cent had one copy of the e4 variant, and three per cent had two copies of the e4 variant, known as the ‘e4e4’ genotype.
The e4 variant is a major risk gene for Alzheimer’s – people with one copy have up to a four-fold increased risk and people with two copies have up to a 14-fold risk, compared to those without.
WHY DOES DEMENTIA INCREASE THE RISK OF COVID-19?
The people most at risk of developing severe symptoms if they catch coronavirus are people over the age of 70. The majority of people living with dementia are over 70 years old, which immediately puts them at greater risk.
Studies are being carried out into how the immune system is involved with dementia. Some suggest that the immune system is not functioning properly. It is known already that the immune system is weaker in older people, including in the lungs.
Many people with dementia will struggle to understand what is happening because the part of their brain that forms new memories is impaired. Therefore they may forget to wash their hands more regularly as the Government advises or keep socially distanced.
There has been an increase in deaths of people in the UK that were not directly caused by COVID-19. This could be for a number of reasons, such as being unable to access healthcare.
For people with dementia, the new isolation rules and many other changes in their life – such as a lack of certain foods in supermarkets – can be particularly distressing and may influence their disease progression. Their behaviour may also change as a result of stress.
The researchers gathered data for who had a positive test for COVID-19 during a period when testing was mostly restricted to hospital patients. Therefore a positive result was a marker of severe COVID-19 infection.
Having the e4e4 genotype raised the risk of severe COVID-19 2.3-fold compared to e3e3, the findings showed. Having just one copy of the e4 variant raised the risk by 14 per cent.
The prevalence of e4e4 in the group that had severe COVID-19 was disproportionately high.
Although less than three per cent of the participants had the e4e4 genotype, six per cent of the 622 people with severe COVID-19 had the e4e4 genotype, while 64 per cent had e3e3.
It suggested people with dementia who have died of COVID-19 may have died as a result of their genetics putting them more at risk – not because dementia makes them more vulnerable, the team said.
First author of the paper Dr Chia-Ling Kuo said: ‘This is an exciting result because we might now be able to pinpoint how this faulty gene causes vulnerability to COVID-19. This could lead to new ideas for treatments.
‘It’s also important because it shows again that increasing disease risks that appear inevitable with ageing might actually be due to specific biological differences, which could help us understand why some people stay active to age 100 and beyond, while others become disabled and die in their sixties.’
The team has previously found that people with dementia are three times more likely to get severe COVID-19.
Professor David Melzer, who led the team, said: ‘Several studies have now shown that people with dementia are at high risk of developing severe COVID-19.
‘This study suggests 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.
‘The effect could be partly due to this underlying genetic change, which puts them at risk for both COVID-19 and dementia.’
It’s difficult to unravel exactly why a person with dementia is more likely to develop COVID-19 because there are so many influencing factors.
Scientists were cautious to draw conclusions from the findings because they cannot rule out that dementia itself caused the COVID-19, and not the genetics.
Dr Chia-Ling Kuo removed people from the sample who had a dementia diagnosis so they could focus solely on genetics with the help of GP records from 2017.
They found the risk of COVID-19 remained in those with the e4e4 gene. EXPLAIN THIS CLEARER
But experts warned it wasn’t possible to completely emit those people from the data, and the disease could have developed in the past three years.
Professor David Curtis, a geneticist at University College London, 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.
‘The study authors try to exclude this possibility by removing subjects who had dementia at the time of recruitment to UK Biobank or recorded on a hospital discharge diagnosis but, perhaps unsurprisingly, very few people meet these criteria.
‘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. I would want to see this tested in a sample where dementia could be more confidently excluded, perhaps a younger cohort.’
Having the e4e4 genotype raised the risk of testing positive for the virus 2.3-fold compared to e3e3, the findings show. Three per cent of participants had the e4e4 gene (9,022). But the prevalence of e4e4 in the group that had tested positive for SARS-CoV-2, the virus which causes COVID-19, was disproportionately high. Six per cent of the 622 people who had a positive test result for the coronavirus had e4e4 (37)
The team tried to remove people from their sample who had a dementia diagnosis so they could focus solely on genetics. They found the risk of COVID-19 remained in those with the e4e4 gene (2.39)
Dr Carol Routledge, director of research at Alzheimer’s Research UK, said: ‘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.’
Despite reservations about the early research, Professor Tara Spires-Jones, UK Dementia Research Institute Group Leader, was impressed with the study.
She said: ‘This study is robustly conducted, and the observation is important and will lead to future research into how APOE4 may influence the risk of contracting COVID-19 or having severe symptoms requiring hospitalisation, where most tests are performed.
‘This is interesting because recent research into why APOE4 also increases the risk of Alzheimer’s disease indicate that APOE4 is involved in the immune system.’
The workings of the immune system have implications for how the body fights the coronavirus, and can be altered by a number of conditions such as obesity, diabetes and possibly dementia.
Dr Fiona Carragher, the Alzheimer’s Society, said more research must uncover why those with dementia have been so badly hit by the coronavirus.
‘Dementia is the most common pre-existing condition, accounting for a quarter of deaths so far, and tragically there’s an additional huge unexplained rise in deaths recorded to dementia alone,’ she said, referencing the high number of excess deaths in care homes that were not directly as a result of COVID-19.
‘People with dementia and their families are desperately worried. The Government needs to take urgent action putting people with dementia at the heart of a clear plan to protect those at risk.’