'It totally backfired': The pitfalls of Alzheimer's genetic testing
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[April 21, 2023]
By Julie Steenhuysen
CHICAGO (Reuters) - Wendy Nelson watched her mother slowly die of
Alzheimer's disease, unable to move or swallow at the end. "All her
pleasures of life were gone," Nelson said.
Grief-stricken, terrified of facing the same death, Nelson ordered
23andMe DNA test kits for Christmas 2020 for herself and three adult
daughters.
A Boston-based biotech executive who is 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 the risk
of Alzheimer's, which means her risk of developing the disease is eight
to 12 times higher than people with the most common version of APOE.
"It totally backfired," she said.
Millions of Americans are expected to test for Alzheimer's in the coming
years – some like Nelson, with at-home test kits, others at labs, as new
drugs for people with early Alzheimer's from partners Eisai Co Ltd and
Biogen Inc and Eli Lilly and Co usher in sweeping change in approaches
to treatment of the disease.
Testing for the APOE4 gene variant among Americans being treated for
Alzheimer's has more than doubled from a year ago, an exclusive analysis
of medical records for Reuters by health data firm Truveta found. The
increase was driven by the new treatments that promise to slow the
progression of the disease, but also carry risks, especially for people
like Nelson carrying two copies of APOE4.
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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
caregivers face a shortage of genetic counselors to explain the tests
and help them navigate the psychological, medical, financial and legal
consequences.
Eisai and Biogen's Leqembi, which arrived on the market in January,
costs $26,500 a year and is not covered by Medicare outside of clinical
trials. Medicare has said it will expand coverage if the drug is granted
full U.S. approval, expected this summer.
"When you learn that information, you're potentially learning
information about your siblings, about your children," said Emily
Largent, a bioethicist and health policy expert at the University of
Pennsylvania Perelman School of Medicine.
"People describe feeling existential dread."
As a scientist, Nelson understood intellectually what her APOE4 results
meant, but they created emotional havoc for her family.
She had inherited one copy of APOE4 from her mother and the other from
her 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 had
to have the disease, because of her genetic test results.
The tests also showed that each of Nelson's three adult daughters had
one copy of APOE4, which triples or quadruples the risk of developing
the disease - confronting them with their own Alzheimer's risks along
with their mother's.
Nelson's daughter, Lindsey, 22, and a fourth year nursing student at New
York University, said she was traumatized when, even before testing,
Nelson talked about exploring assisted suicide rather than suffer her
mother’s fate.
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"I would yell at her, cover my ears and run away," Lindsey said. "There
are many complicated emotions involved."
Nelson's eldest daughter, Lexi, 24, who works in data analytics, turned
to research showing that lifestyle changes such as weight lifting can
improve cognitive function. "I've tried really hard to improve my sleep,
I’m exercising a lot," she said.
Her youngest, Pam, 20, a sophomore biology major at UCLA, said she takes
comfort in knowing that her mother's result is not a diagnosis. "It's
just a risk factor, and there are many other factors that influence what
will happen."
Leqembi is not suitable for Nelson, who is not symptomatic. Even if she
were eligible, she said she is not a fan because of the risk of brain
swelling, which is higher for people with two copies of APOE4.
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![](../images/042123PIX/health27.jpg)
Wendy Nelson does a puzzle at her home
in Foxborough, Massachusetts, U.S., March 21, 2023. REUTERS/Brian
Snyder
![](http://archives.lincolndailynews.com/2019/Sep/05/images/ads/current/stclara_lda_SPONSOR_090519.png) Nelson is pinning her hopes on an
experimental pill from Alzheon Inc, which is being tested in people
with early Alzheimer's who have two copies of APOE4.
She is working her way through a bucket list of
trips. In February, she climbed Mt. Kilimanjaro to raise money for a
cancer charity, and she would like to visit Patagonia, the Greek
Islands, South Africa, possibly Antarctica.
If treatment fails, she said she has her "exit plan": legal
euthanasia through a clinic in Switzerland. "I do not want to live
the way my mom had to live her last five years of life. She was
miserable," she said.
THE TESTING REVOLUTION
Until recently, most doctors tended not to order genetic tests to
determine Alzheimer's risk, because there were no effective
treatments to slow or prevent the disease.
That changed with Leqembi, which was 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 buildup in the brain of amyloid plaques
associated with Alzheimer's, and are viewed 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, it behooves us to check," said Dr. Sarah Kremen, a
neurologist at Cedars-Sinai in Los Angeles.
In the four months ahead of U.S. approval of Leqembi in January,
APOE4 testing among people over 55 who visited a doctor within the
last 30 days increased 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 in the same period a year earlier, the
analysis by Seattle-based Truveta found.
The analysis was based on a review of medical records from 7.9
million adults at 28 major U.S. hospital systems. It does not
include at-home consumer tests.
The National Institutes of Health estimates up to 25% of people in
the United States have one copy of APOE4 and up to 5% have two
copies.
![](http://archives.lincolndailynews.com/2023/Apr/21/images/ads/current/humanesociety_sda022411.png)
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 the
U.S. had just one trained genetic counselor per 82,000 people. The
United Kingdom had 1 per 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 being 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,
Banner's director.
While the U.S. Genetic Information Nondiscrimination Act (GINA) bans
discrimination in employment and health insurance, it does not cover
long-term care and disability and life insurance.
Some members of families with increased genetic risk of Alzheimer's
say it might be better not to know at all.
Dovie Bryant, 77, who is taking part in the Lilly trial, lost her
mother to Alzheimer's in 2012.
When she shared with her five siblings that she had one copy of the
APOE4 variant, none wanted to find out their own status.
Her brother Jim Painter, 71, said he feared testing could make it
harder to pass a health screening to move into a retirement
community that offers increasing levels of care as a person ages.
"That might be a red flag," Painter said.
(Reporting by Julie Steenhuysen; editing by Caroline Humer and
Suzanne Goldenberg)
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