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Nearly Everyone With Mild Cognitive Impairment Goes Undiagnosed
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Celia Ford

Science
Nov 13, 2023 7:00 AM


NEARLY EVERYONE WITH MILD COGNITIVE IMPAIRMENT GOES UNDIAGNOSED

Millions of older adults likely have minor memory issues that can later become
dementia. But only a fraction of them are diagnosed early enough for new
treatments to stand a chance.
CT scans showing brain atrophy associated with Alzheimer's disease.Photograph:
Callista Images/Getty Images

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Millions of people over the age of 65 likely have mild cognitive impairment, or
MCI—minor problems with memory or decisionmaking that can, over time, turn into
dementia. But a pair of recent studies both concluded that 92 percent of people
experiencing MCI in the United States are not getting diagnosed at an early
stage, preventing them from accessing new Alzheimer’s treatments that may be
able to slow cognitive decline if it’s caught soon enough.

“We knew it was bad. But we didn’t know it was that bad,” says Ying Liu, a
statistician at the University of Southern California Dornsife's Center for
Economic and Social Research and a researcher on both studies.

In the first, published this summer in Alzheimer’s Research & Therapy, Liu’s
team aimed to figure out how often MCI is being diagnosed—and how often it’s
overlooked. Using data from the Health and Retirement Study, a longitudinal
survey of some 20,000 people in the US about a wide range of age-related
factors, Liu built a model predicting the number of expected MCI diagnoses for
the over-65 population overall: about 8 million. Then, Liu’s team pulled data
from all Medicare beneficiaries aged 65 and up who were enrolled from 2015 to
2019, to see how many were actually diagnosed with the condition. They found
that only 8 percent of the people whom their model predicted would be candidates
for MCI, based on their health demographics, actually received a diagnosis. This
number was even lower for Black and Hispanic beneficiaries and among
lower-income people. (The team used eligibility for Medicaid, health coverage
that supplements Medicare, as a marker of income status.)

A second study, published in October by Liu’s team, looked at Medicare claims
submitted by 226,756 primary care physicians and compared their MCI detection
rates with those predicted by their model. Again, they found that only about 8
percent of predicted cases were actually diagnosed, and only 0.1 percent of
clinicians diagnosed the condition as often as the team calculated that they
should.



Autopsies reveal that most people who die in old age have some kind of brain
pathology that impairs cognition, from traces of stroke to the amyloid plaques
that characterize Alzheimer’s. Not everyone who has these anatomical markers of
neurodegeneration experiences memory problems, but “the more of these things you
have in your brain, the more likely you are to manifest dementia,” says Bryan
James, an epidemiologist at the Rush Alzheimer’s Disease Center, who was not
involved in this research. If someone does experience problems like forgetting
who family members are, or getting lost while walking familiar paths, a
combination of cognitive tests, brain scans, blood work, or a spinal tap can
pinpoint the cause of their dementia.

Diagnosing mild cognitive impairment is much trickier. People might notice that
something is off, but they’re still able to function independently. Most are
seen by primary care physicians, not researchers in specialized memory care
clinics. Because these doctors don’t see many dementia patients, their
confidence in giving someone a potentially life-shattering diagnosis can be low.
“They don’t want to make a mistake,” says Sarah Kremen, a neurologist at the
Jona Goldrich Center for Alzheimer’s and Memory Disorders, who was not involved
in this research.



“We are still struggling, as a healthcare profession, with how to best identify
mild cognitive impairment,” adds primary care physician Barak Gaster, who is
also a professor of medicine at the University of Washington. Many doctors in
Gaster’s field know they lack the training to handle cognitive concerns, and
they are eager to learn. However, annual Medicare wellness visits are
time-constrained—often just 60 minutes—and cover a lot of ground. Cognitive
assessments are too cursory to detect the subtleties of MCI. “It’s really
challenging to ask a community health provider to do another thing, because
they’re already doing everything,” says Nancy Berlinger, a senior research
scholar at the Hastings Center, an independent bioethics research institute in
New York. Plus, people generally don’t want to be told they have memory
problems. “Because of the stigma surrounding dementia, primary care providers
may just avoid the topic,” says Berlinger.

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“We’re failing a lot of people,” says Sarah Banks, a neuropsychologist at the
University of California, San Diego, and director of the neuropsychology program
of their Memory Disorders Clinic. “I’m not surprised that it’s being
underdiagnosed, but I was surprised by how much.”



Even if both the doctor and the patient notice something is off, Gaster adds,
“the elephant in the room is that, if a cognitive concern comes up, most primary
care providers still aren’t sure what to do.” Until very recently, an MCI
diagnosis didn’t come with any actionable treatment options—just the knowledge
that a patient may develop dementia someday. The same question has plagued
efforts to develop blood tests for Alzheimer’s risk: Will they unnecessarily
stress a person who can do little to change their outcome?



But this summer, the US Food and Drug Administration approved the new
Alzheimer’s medication lecanemab-irmb, or Leqembi, which clears amyloid plaques
from the brain and slows the progression of cognitive decline. Liu calls it “a
big game changer.” Donanemab, another potential treatment developed by
pharmaceutical company Eli Lilly, also reduced amyloid levels and slowed
cognitive decline in Phase 3 clinical trials of people with early-stage
Alzheimer’s disease.

While these new medications are a big deal, “they’re not a panacea,” Kremen
cautions. In Phase 3 clinical trials, lecanemab slowed cognitive decline by 27
percent over the 18-month study, a relatively modest improvement. And it’s not
an easy treatment—patients need infusions at a clinic every two weeks. The drug
can have potentially life-threatening side effects like brain swelling and
seizures. As a consequence, “I think a lot of us in the field are a little
skeptical about how helpful they’ll be,” Banks says. James adds, “There’s a
risk-benefit balance that I don’t think we’ve worked out yet.”

Drug treatment also depends on early detection. Amyloid plaques kill brain
cells, which can’t grow back. If you don’t try to get rid of the plaques until
they’ve already killed a bunch of cells, James says, “You’re trying to put out a
fire after the house burned down.”

More clinical testing will be necessary to determine exactly how effective these
drugs will be for people who start taking them as early as possible. “Dementia
is not a problem that we can quickly solve through a pill,” Berlinger says, but
“we may be in an era of promising interventions in early stages, which rely on
the ability to detect early symptoms.”

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Still, James predicts that in five years, as these treatments become more
effective and accessible, the diagnostic rate for MCI will skyrocket.
“Diagnostic practices are driven by the availability of treatment,” he says.
“People don’t just diagnose in a vacuum. They diagnose for a purpose.”

Even if these treatments work, the US healthcare system is not currently
equipped to handle the demand for them. Lecanemab currently costs $26,500 per
year, and Medicare covers 80 percent of the cost. If all of the people whom
Liu’s studies estimate are experiencing mild cognitive impairment are diagnosed
and seek treatment, James says, “it would bankrupt Medicare.” Memory clinics
will also struggle to handle the onslaught of referrals. (Rush Memory Clinic,
where James works, already has a yearlong waitlist.)

These studies were limited to demographic basics like age, sex, race, and
Medicaid eligibility. Age is one of the greatest risk factors for developing
MCI—the older you are, the more likely you are to have it. Autopsy studies also
show that women seem to develop neuropathology linked to dementia more than men,
but in Liu’s studies, detection rates were not dramatically different across
sexes or age groups.

Race, however, was one of the strongest predictors of whether or not MCI is
accurately diagnosed, with Black people getting diagnosed at half the rate of
white people. It’s unclear whether the stark racial divide in detection rates
Liu’s team observed is due to differences in MCI prevalence itself, or to
differences in healthcare access. Cognitive screening measures were largely
developed by white people, for white people, Banks says, likely reducing their
sensitivity in other populations. Factors like lower-quality childhood
education, the chronic stress of systemic racism, and lack of access to healthy
food can all contribute to dementia risk, James adds. Liu’s team is currently
building predictive models that account for more of these factors.



Even if a person’s MCI never escalates into full-blown dementia, doctors say
there is value in screening for it, because it can let them help alleviate
symptoms or weed out other possible confounding causes. For example, doctors can
review medications with patients to make sure nothing they are taking lists
brain fog as a side effect. Hearing loss is a major contributor to dementia
risk, and doctors can help people access hearing aids. Basic lifestyle changes
like eating well, exercising, getting good sleep, and nurturing social
connections address both brain health and overall well-being.

Doctors need to normalize talking about brain health with patients of all ages,
says Elizabeth Head, a program manager at the Georgia Department of Public
Health, who led their campaign for early detection of dementia. “We don’t have
to ‘break the ice’ to talk about heart disease, cancer, or other chronic
conditions,” she says. “It should be talked about like any other type of
disease.”

Update 11-13-2-2023 1:36 pm: This story was updated to correct Sarah Banks' job
title and the time allotted to Medicare wellness visits.






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Celia Ford is a freelancer based in the San Francisco Bay Area and formerly a
WIRED AAAS Mass Media fellow. She received a PhD in neuroscience from the
University of California, Berkeley, and writes about biotech, brains, and
whatever makes people think about thinking.
Contributor

Topicspublic healthNeurosciencememoryhealthhealthcaremedicineBrains and
Behaviordiseasesagingdoctors
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