Carol is the latest in generations of her family to die from Alzheimer’s.
Now her grieving children face the awful dilemma: Should they be tested... or is it best not to know?
IN THE 1980s, Nottingham schoolteacher Carol Jennings penned a short letter which changed the way the world understood Alzheimer’s dementia. ‘I think my family could be of use,’ it began. Many years and billions of pounds in research funding later, it would lead to the first effective drugs for the degenerative brain disease which have recently emerged. Carol’s letter, to top neurologist Professor John Hardy, detailed how her family had been blighted by dementia.
Her 63-year-old father Walter had it, she wrote, ‘as does his sister, Audrey. His brother, Arthur, also may have the disease.’
At the time, relatively little was known about Alzheimer’s aside from that it was seen as an inevitability of old age for some. ‘My doctor keeps telling me it doesn’t run in the family but... it clearly does,’ Carol’s letter continued.
Prof Hardy says Carol’s letter was a watershed moment. ‘We’d been trying to find genetic mutations that might lead to Alzheimer’s for some time,’ he recalls. ‘So we put out an advert in the Alzheimer’s Society newsletter looking for families with a strong history of the disease. Carol’s letter was the first response I read.’
The researchers took blood samples from the Jennings family and, several years later, concluded that many of them carried the same
I kind of overthink everything that could be a symptom
genetic defect – which triggered a rare hereditary form of Alzheimer’s.
These remarkable events will feature in a BBC Two documentary which followed Carol, who died late last month aged 70, and her close relatives for two-and-a-half years. The Jennings Family vs Alzheimer’s, which airs of May 13, also reveals that Carol’s two children, John and Emily, are still grappling with the decision to take a blood test to find out whether they carry the genetic defect.
They have a 50/50 chance of having the DNA fault, as they may have inherited a healthy copy of the gene from their father who isn’t affected. The siblings John, 38, and Emily, 42, fear, quite understandably, that finding out their risk would change their lives forever.
In Emily’s case, it would also mean telling her eight-year-old daughter Eleanor that she could develop Alzheimer’s at a young age. The siblings have put off the decision because, until now, there was nothing that could be done to stop the degenerative brain disease.
But, with the UK approval of two Alzheimer’s treatments expected any week now, that could soon change. John, a teacher who lives in Edinburgh with his husband Matt, describes the dilemma as ‘the most difficult decision in my life’.
‘The desire to have the test has always kind of ebbed and flowed,’ he says. ‘I don’t have any plans for getting old because I don’t imagine that I will. At the moment, I kind of overthink everything that could be a symptom of my brain changing.
‘You can’t help but think maybe it’s already happening for me. My biggest fear is losing my connections to people around me. I think that’s the thing that I’m scared of, being alone in a scary place.’
Emily, who lives near Leicester, says she is ‘pretty much in denial’ about her Alzheimer’s risk.
‘As I’ve got older, and I’ve had Eleanor, there’s even more to think about, because it has a knock-on impact on her,’ she says. ‘If I’m getting it, she has a 50/50 chance of getting it. I don’t want her thinking about it I suppose.’
But she says: ‘I feel like I don’t worry about anything else apart from that. I never go past the next year or two in my mind.’
Emily adds that her husband Mark has repeatedly urged her to get the test, telling her ‘you’re living your life like you’re going to get [Alzheimer’s] anyway’.
Experts say the dilemma John and Emily face is representative of the rapidly changing nature of Alzheimer’s care. The Jennings family genetic defect means their immune systems are unable to clear a toxic protein from the brain – called amyloid plaque.
Researchers concluded that, over time, this plaque builds up in the brain, triggering Alzheimer’s.
The genetic defect carried by Carol and her family is exceedingly rare. Fewer than 100 people in the UK today are thought to have it. However, the study they participated in was revolutionary because it was the first to pinpoint a cause of Alzheimer’s – amyloid plaque.
Researchers noticed during postmortums that the brains of all deceased Alzheimer’s patients were covered in these tangled proteins – regardless of whether they carried this rare genetic defect.
Four decades and thousands of studies later most experts now believe Alzheimer’s cases are caused by a buildup of amyloid.
And, in 2022, it was announced that two drugs that removed amyloid from the brain were capable of slowing the progress of Alzheimer’s by as much as a third – opening up the possibility of a cure.
Both medicines, lecanemab and donanemab, are given via an infusion every two weeks. They are designed to seek out and destroy amyloid plaque in the brain.
When the results from the lecanemab study were published at the end of 2022, some doctors hailed it as ‘the beginning of the end’ for Alzheimer’s. However, the treatments are not without controversy. Both drugs have a high rate of side effects. About one in ten trial participants experienced swelling in the brain and one in six had brain bleeds.
Three patients on the lecanemab trial died as a result of suspected side effects. There were four side effect-related deaths on the donanemab trial. The medicines are also costly. An NHS report published in February suggested that rolling out lecanemab and donanemab would cost the Health Service up to £1billion a year.
Moreover, both treatments are most effective when given to patients in the earliest stages of Alzheimer’s. Currently, there is no effective test to catch the condition early meaning most Britons with Alzheimer’s would be diagnosed too late to benefit. However, experts say the fact the drugs can slow Alzheimer’s at all means there is hope that, in the coming years, even more effective – and safe – amyloid-attacking medicines will be developed. Earlier this year, UK scientists also announced they had successfully developed a blood test which could spot Alzheimer’s – meaning patients could also eventually be diagnosed much earlier, limiting the damage caused by amyloid.
‘We are in the treatment phase now for Alzheimer’s disease,’ says Dr Cath Mummery, a dementia expert at University College London. ‘We have a drug. It has a modest effect. It’s not the magic bullet that’s going to completely reverse the disease. But it’s the foundation stone that we can build on.’
Experts say new Alzheimer’s treatments raise hopes for patients most at risk of the disease.
While the genetic amyloid defect carried by many of the Jennings family is exceedingly rare, it is not the only early warning sign of the disease. Research suggests around a quarter of the population carry one copy of a gene called APOE4 which doubles their chances of developing Alzheimer’s.
Around 3 per cent of people have two copies of APOE4 which can increase the risk of the disease by
It’s too late for Carol, but hopefully not for Emily and John
as much as eight times. In 2022, Australian actor Chris Hemsworth, star of the Thor films, revealed he had taken a gene test that showed he had two copies of APOE4.
However, for these patients there has been very little that could be done to protect them against Alzheimer’s once it arose.
Prof Hardy believes that amyloid plaque will eventually be treated like high cholesterol, which can be tackled with a daily statin to stop heart attacks or strokes ever occurring.
‘You don’t wait to have a heart attack to start taking a statin,’ says Prof Hardy. ‘I think the same will happen with amyloid drugs. People who are at risk of the disease will start taking them early before the symptoms occur.’
He added: ‘If you’d asked five years ago whether I thought it was worth testing for APOE4 I would have said it wasn’t worth it, because there was nothing you could do. But now with treatments available, which will only get better, I think knowing your risk is much more valuable.’
John Jennings says the arrival of the two new Alzheimer’s drugs makes him feel more optimistic about the future – and could swing him towards getting the test. ‘It actually feels like I’ve got more time,’ he says. ‘It’s taken some of that pressure off. It’s so great to see it actually happening.’
He adds that it makes him feel ‘optimistic’ his niece Eleanor’s generation will have an even better chance, as amyloid drugs continue to improve. However, his sister Emily says she is still unlikely to find out her risk of Alzheimer’s because she frets about what testing positive would mean for Eleanor.
‘I’d get upset more or I’d worry more about Eleanor,’ she says. ‘I’d want Eleanor to have the test because I’d want to know whether I’d given it to her. I’m in denial. I definitely don’t want to think about it. I do worry if I have any sort of symptom, like cloudy brain. I think this could be the start of it.’
John and Emily’s father, retired vicar Stuart, 66, says he hopes his children get tested – and believes it is what Carol would have wanted.
‘It’s too late for Carol I’m afraid, but hopefully not Emily and John,’ he says. ‘This is what Carol’s been working for for over 30 years.’