05.2020 | THE SCIENTIST 53Early diagnosis could not only aid
intervention for people at high risk of
developing dementia, but provide better
opportunities to design new therapies,
says Routledge. “If we were able to diag-
nose early, then that might start telling us
what goes wrong in the very early stages,”
she says, “which in turn might help us get
insight into more appropriate targets that
we could eventually develop treatments
for.” Pharmaceutical companies might be
able to work with populations of at-risk
individuals to re-examine failed drugs that
didn’t work in people with later stages of
the disease. “We likely might even already
have some of those treatments, it’s just that
we are not stratifying [the patient popu-
lation] at the precision level that allows
them to work as effectively as they could,”
says Rhoda Au, a neuropsychologist at
Boston University School of Medicine.
That’s why researchers at Evidation
and its collaborators, who published the
findings of their smart-device study last
year, are so interested in harnessing the
power of wearable or mobile technology.
By passively gathering data from people
not yet showing obvious clinical symptoms
of cognitive decline, these devices could
be used to create a digital phenotype that
helps clinicians diagnose dementia early,
before neuronal death.
Evidation isn’t the only company
interested in harnessing these 21st-century
communications technologies to try to
address neurodegeneration. Pharma com-
panies are incorporating digital technolo-
gies in their own research, trying to develop
in-house solutions, says Au, and many ven-
ture firms and other funders are now back-
ing such efforts. Last April, the Alzheimer’s
Drug Discovery Foundation put out a call
for proposals on digital biomarkers of the
disease and related dementias, and the US
National Institute on Aging is also fund-
ing research in this area. Earlier this year,
Alzheimer’s Research UK launched EDoN
(Early Detection of Neurodegenerative dis-
eases), a global initiative that will develop
“digital fingerprints” of conditions such
as Alzheimer’s to “revolutionise the early
detection of neurodegenerative diseases,”
according to a press release.
With all the investment in digital bio-
markers of early cognitive decline, says
Au, “I think... collectively, we are going
to start to have these solutions emerge.”Early days
Fortunately for the research community,
members of the public are keen to monitor
their health, as evidenced by the more than
300,000 health-related apps and 340 wear-
able devices already available as of 2017,
according to a report by health-focused data
science company IQVIA. Many apps purport
to detect cognitive decline using data on a
user’s movement, cognition, and other factors
that may begin to slide years before that per-
son would fail a clinical test for dementia.There’s science to support the idea
that subtle changes can precede dementia.
Studies have found, for example, that
around 12 years before a clinical diagnosis
of mild cognitive impairment, a person’s gait
begins to slow dramatically. Other research
has shown that, compared with healthy
controls, patients suffering from mild cog-
nitive impairment have a higher blink rate
and lower heart rate variability. Circadian
rhythm disruptions also seem to occur in the
very early stages of cognitive decline. But by
themselves, these small changes are unreli-
able markers of neurodegenerative disease.
Few of the apps and devices on the market
have been validated by rigorous research;
none are FDA-approved.
The study conducted by Evidation
and its collaborators aimed to provide
real predictive ability by aggregating data
from the sensors in multiple devices, as
well as basic device usage metrics—how
often phones were locked and unlocked,
and numbers of calls and texts—to evalu-
ate cognitive status. Researchers looked
at gross motor function using acceler-
ometers, pedometers, and gyroscopes;
heart rate using the heart rate monitor ina smartwatch; circadian rhythms using
Beddit sleep sensors; various behavioral,
social, and cognitive characteristics mea-
sured by app usage, phone use behavior,
and text message and phone call metadata;
fine motor control using an iPad assessment
app for typing and dragging tasks; and lan-
guage skills using the iPad app.
Through these devices, the research-
ers monitored 113 people between the
ages of 60 and 75 years old—31 people
with cognitive impairment (as deter-
mined by standard criteria) and 82 with-
out. Once generated, participants’ data
arrived encrypted at Evidation’s Study
Platform, where they were time-stamped,
stored, and analyzed. The team found
some important differences between the
groups of subjects. For example, partici-
pants with cognitive decline typed more
slowly and had more pauses during typ-
ing, perhaps because of fine motor prob-
lems or language difficulties or both, the
researchers reported last summer. Those
with cognitive impairment also walked in
a less regular pattern, and their first steps
came later in the d ay. They sent fewer
text messages, had a greater reliance on
helper apps such as the Clock app, which
tells the time and sets alarms, and were
more likely to use Siri’s app suggestions.
The researchers used machine learn-
ing on the dataset to develop a model to
distinguish which people had cognitive
impairment and which were healthy,
based solely on the pattern of digital
data received from the participants’
devices and their responses to iPad
tasks. The resulting model was able to
distinguish between healthy individuals
in that dataset, those who had mild cog-
nitive impairment, and those with mild
Alzheimer’s disease, with an accuracy
similar to that of computerized cognitive
tests administered in clinical settings.
“[Eli] Lilly [working with Evidation]
has done a lot of good work there,” says
Graham Jones, director of innovation
at Novartis Technical Research and
Development, who has researched digi-
tal biomarkers and wearable devices for
Alzheimer’s disease but wasn’t involved
in the study.We know nothing, or very,
very little, about early-
stage disease.
—Carol Rout ledge, Alzheimer’s Research UK