CHICAGO, April 21 (Reuters) – Wendy Nelson watched as her mother slowly died of Alzheimer’s, unable to move or swallow at the end. “All the pleasures of her life were gone,” Nelson said.
Grief-stricken, terrified of facing the same death, Nelson ordered 23andMe(ME.O) DNA test kits for Christmas 2020 for herself and three adult daughters.
A Boston-based biotech executive now 52, Nelson hoped the kits would provide reassurance. They delivered the worst possible result. Nelson has two copies of the APOE4 gene variant that increases Alzheimer’s risk, meaning his risk of developing the disease is eight to 12 times higher than in people with the more common version of APOE.
“It totally failed,” he said.
Millions of Americans are expected to be tested for Alzheimer’s in the coming years, some like Nelson, with home testing kits, others in labs, as new drugs for people with early Alzheimer’s from partners Eisai Co Ltd (4523.T) and Biogen Inc (BIIB.O) and Eli Lilly and Co (LLY.N) usher in a radical shift in approaches to treating the disease.
Testing for the APOE4 gene variant among Americans being treated for Alzheimer’s has more than doubled from a year ago, according to an exclusive analysis of medical records for Reuters by health data company Truveta. The rise has been driven by new treatments that promise to slow the progression of the disease but also carry risks, especially for people like Nelson who carry two copies of APOE4.
Yet few support services are available to help people deal with the implications of APOE4 testing, according to interviews with more than a dozen neurologists and genetic counselors. Alzheimer’s patients and healthcare professionals face a shortage of genetic counselors to explain testing and help them navigate the psychological, medical, financial and legal consequences.
Eisai and Biogen’s Leqembi, which hit the market in January, costs $26,500 a year and isn’t covered by Medicare outside of clinical trials. Medicare has said it will expand coverage if the drug receives full U.S. approval, expected this summer.
“When you learn this information, you are potentially learning information about your siblings, your children,” said Emily Largent, a bioethicist and health policy expert at the University of Pennsylvania’s Perelman School of Medicine.
“People describe feeling existential dread.”
As a scientist, Nelson understood intellectually what her APOE4 results meant, but they wreaked emotional havoc on her family.
He had inherited one copy of APOE4 from his mother and the other from his father, who was showing no symptoms of Alzheimer’s at the time.
When her father’s memory began to fail a year later, one of her two sisters doubted it could be Alzheimer’s, Nelson said. Nelson knew he must have the disease, due to the results of his genetic tests.
Tests also showed that each of Nelson’s three adult daughters had a copy of APOE4, which triples or quadruples their risk of developing the disease, pitting them against their own Alzheimer’s risks alongside their mother’s.
Nelson’s daughter, Lindsey, 22, and a fourth-year nursing student at NYU, said she was traumatized when, even before the test, Nelson spoke of exploring assisted suicide rather than suffer the fate of his mother.
“I would yell at her, cover my ears and run,” Lindsey said. “There are a lot of complicated emotions involved.”
Nelson’s eldest daughter, Lexi, 24, who works in data analytics, turned to research showing lifestyle changes like weight lifting can improve cognitive function. “I’ve been really trying to improve my sleep. I’m exercising a lot,” she said.
His youngest, Pam, 20, a sophomore in biology at UCLA, said she finds comfort in knowing her mother’s result isn’t a diagnosis. “It’s just one risk factor, and there are many other factors that influence what’s going to happen.”
Leqembi is not suitable for Nelson, who is not symptomatic. Even if it were eligible, she said she’s not a fan because of the risk of brain swelling, which is higher for people with two copies of APOE4.
Nelson is pinning his hopes on an experimental pill from Alzheon Inc, which is being tested on people with early Alzheimer’s who have two copies of APOE4.
It’s working its way through a list of must-see trips. She climbed Kilimanjaro in February to raise money for a cancer charity and would like to visit Patagonia, the Greek Isles, South Africa, possibly Antarctica.
If treatment fails, she said she has her own “exit plan”: legal euthanasia through a clinic in Switzerland. “I don’t want to live the way my mother had to live her last five years of her life. She was unhappy,” she said.
THE TEST REVOLUTION
Until recently, most doctors tended not to order genetic testing to determine Alzheimer’s risk, because there were no effective treatments to slow or prevent the disease.
That has changed with Leqembi, which has been shown to reduce the rate of cognitive decline by 27% in patients with mild Alzheimer’s. Eli Lilly’s donanemab is in clinical trials with results expected by June.
Both drugs remove the accumulation of amyloid plaques in the brain associated with Alzheimer’s and are seen as a first step towards even more effective treatments. Both can cause swelling and microbleeds in the brain. US regulators recommend genetic testing before starting treatment with Leqembi.
“With this drug, we’d better check,” said Dr. Sarah Kremen, a neurologist at Cedars-Sinai in Los Angeles.
In the four months leading up to Leqembi’s US approval in January, APOE4 testing among people over the age of 55 who visited a doctor in the past 30 days increased by 125%. From September 2022 to January 2023, the rate averaged 1.4 tests per 100,000 patients, compared with 0.6 tests per 100,000 patients during the same period a year earlier, according to the Seattle-based Truveta analysis.
The analysis was based on a review of the medical records of 7.9 million adults in 28 major US hospital systems. Does not include home consumer testing.
The National Institutes of Health estimates that up to 25% of people in the United States have one copy of APOE4 and up to 5% have two copies.
Yet there is a shortage of genetic counselors to help families deal with the implications of having two copies of APOE4.
A 2018 study in the European Journal of Human Genetics found that the United States had only one qualified genetic counselor for every 82,000 people. The UK had 1 in 193,500.
Banner Alzheimer’s Institute in Phoenix, which is testing Lilly’s donanemab, is researching an interactive online platform to deliver APOE results to volunteers screened for enrollment in the trial.
“We needed a scalable way to warn people about the potential benefits and risks of genetic disclosure,” said Dr. Eric Reiman, director of Banner.
While the US Genetic Information Nondiscrimination Act (GINA) prohibits discrimination in employment and health insurance, it does not cover long-term care, disability, and life insurance.
Some members of families with an increased genetic risk of Alzheimer’s say it may be better not to know at all.
Dovie Bryant, 77, who is taking part in the Lilly trial, lost his mother to Alzheimer’s in 2012.
When he shared with his five siblings that he had a copy of the APOE4 variant, no one wanted to find out their status.
His brother Jim Painter, 71, said he feared the tests could make it more difficult to pass a health screening to move into a retirement community that offers increasing levels of care as a person ages.
“It could be a red flag,” Painter said.
Reporting by Julie Steenhuysen; editing by Caroline Humer and Suzanne Goldenberg
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