The EconomistAugust 29th 2020 Special reportDementia 51P
erforming his autopsy on Auguste Deter in 1906, Alois Alz-
heimer noticed three unusual features of her brain. It was at
least a third smaller than normal. Many neurons, the nerve cells,
had vanished. He also saw abnormal deposits inside the remain-
ing cells, especially in the cerebral cortex, the thin outer layer of
grey matter. Between a third and a quarter had been invaded by
dense knotty bundles, now known as “neurofibrillary tangles”,
caused by a build-up of a protein called tau. And across the cortex
were deposits of another protein, since identified as beta-amyloid,
which collect between neurons and disrupt their functioning.
Despite decades of research, Alzheimer’s still has no vaccine
and no cure. Some fear that the covid-19 crisis will now squeeze the
financial and scientific resources available for dementia research.
In the pandemic, research has anyway suffered because clinical
trials became difficult. Miia Kivipelto, a Finnish neuroscientist
who led a study showing how changes in ways of life could slow or
arrest cognitive decline, had to suspend her follow-up research.
And many people have become wary of seeking diagnosis or help,
for fear of infection, or of laying claim to health-care resources
needed elsewhere.
Most research into Alzheimer’s has focused on ways to attackone of the proteins, beta-amyloid. The ap-
proach is often called “the amyloid hypoth-
esis”. But it is not known if the proteins
cause the disease or are just among its
symptoms. Many elderly brains have large
accumulations of beta-amyloid and tau,
but no memory loss or other signs of de-
mentia. So proving the hypothesis has been
tricky. Over 200 drugs have been tested, but
not one disease-modifying treatment has
been found. A paper in 2014 by Jeff Cum-
mings, of the Cleveland Clinic at the Lou
Ruvo Centre for Brain Health in Las Vegas,
looked at clinical trials for Alzheimer’s
drugs from 2002 to 2012. The failure rate, he
concluded, was 99.6%.
Four drugs have been developed (three
“cholinesterase inhibitors”, and an “nmda
receptor”) that have limited effects in some
patients. Takeshi Iwatsubo, professor of
neuropathology at the University of Tokyo,
explains that the drugs attack the symp-
toms but not the disease, and can have un-
pleasant side-effects, such as nausea and
diarrhoea. So debatable are the benefits
that in May 2018 the French government
stopped reimbursing payments for them.
Those working on dementia are used to
big drug companies announcing setbacks,
or even that they are giving up—as Pfizer
did in 2018. One problem is that most test-
ing has been conducted on those who al-
ready have the condition, when it may be
too late to stop its advance. Mr Iwatsubo
says the build-up of beta-amyloid precedes the onset of mild cog-
nitive impairment (mci) by 15-20 years. So it was disappointing
when, in February, Eli Lilly and Roche released results from a test
of anti-amyloid drugs among those genetically predisposed to ear-
ly-onset Alzheimer’s. Cognitive tests showed that neither pro-
duced a significant benefit over a placebo.
In March 2019 Biogen, an American firm, and Eisai of Japan an-
nounced that they were ending two clinical trials among people
with mcior early-onset Alzheimer’s. They were testing aducanu-
mab, another anti-amyloid drug. But then, in October, Biogen said
a fresh look at the data showed that the drug had worked in some
cases. “Patients...experienced significant benefits on measures of
cognition and function such as memory, orientation and lan-
guage.” The firm has now applied for approval of the drug by Amer-
ica’s Food and Drug Administration (fda). Last November China
conditionally approved Oligomannate (gv-971), a drug produced
by a company from Shanghai, Green Valley. This was the first drug
to have got so far in the approval process in 17 years. Derived from
marine algae, it was reported to have been shown in trials to reduce
amyloid accumulation and improve cognitive functioning.
Reactions to these new drugs have ranged from the celebratory
(Paola Barbarino, adi’s boss, called the change of mind about adu-
canumab a “ray of sunshine”) to the cynical. The value of Biogen’s
shares, it was noted, fell by nearly 30% the day it declared the trials
a failure and rose by 26% when it said it would seek approval after
all. And the data from the Chinese study, Western scientists grum-
bled, were scanty and its conclusions hard to credit.
Even if a drug is approved, who will pay for it? The worst that
could happen, says Edo Richard, a neurologist at the University of
Amsterdam, is approval of a drug that works a bit for some people.
So prevalent is Alzheimer’s that private and public insurers wouldPlaqueblues
The search for a cure for dementia is not going wellThe science