Eye and smell tests could diagnose Alzheimer’s early (Wired UK)


The eye tests look for signs of beta-amyloid plaque in the retina
The eye tests look for signs of beta-amyloid plaque in the retinaShutterstock


Eye tests could alert physicians
to signs of Alzheimer’s up to two decades before a clinical test
would, while smell tests could also indicate the disease has set
in.

These claims were made by four different research groups during
the annual Alzheimer’s
Association International Conference
being held this week in
Copenhagen. The studies sound fairly incredible, but in each case
two groups have backed up the preliminary findings that these tests
hold promise.

One such test relies on a simple eye examination that indicates
beta-amyloid plaque — a sign of Alzheimer’s — has begun
accumulating in the brain, while the other relies on a reduced
ability to identify smells, which has been linked with loss of
brain cell function associated with the disease. Both approaches
tackle two pertinent problems with Alzheimer’s diagnostics today.
The primary one is that it is not detected earlier enough for
potential interventions to be meaningful enough. The second, is
that tests available now are either highly subjective and time
consuming, or highly invasive.

Doug Brown, Director of Research and Development at Alzheimer’s
Society, said the tests could be a “game changer” for the future of
research. “These studies provide proof of principle that scanning
the eye for amyloid could give us insight about what is going on in
the brain,” he said. “However as they are only preliminary studies,
the eye scans will need further validation before they could be
used on people with dementia.

“We know that the damage caused by Alzheimer’s begins decades
before symptoms appear, so in addition to improving diagnosis we
need more research to find ways to stop it developing in the first
place. One in three people over 65 will develop dementia so finding
answers is one of the most important tasks facing science
today.” 

The road to a diagnosis is currently a long and tricky one. It’s
not until changes have already begun in a person’s behaviour that a
doctor will usually first be consulted. Plenty of other factors
have to first be ruled out, and basic medicals conducted. Cognitive
tests will be administered, before a referral to a specialist is
arranged. A host of psychologists, psychiatrists and neurologists
might be consulted, all taking the individual through more memory
assessments. This will help the team assess the level of impairment
— but still a diagnosis is not made. It is only once the patient
has a CT scan and MRI scan, that doctors can make a more assured
judgement. Even this is mainly designed to rule out other
causes.

It’s only recently that tests for beta-amyloid, a plaque that
builds up in the brains of Alzheimer’s patients, have been
trialled. We know of this build-up because of autopsies carried out
on deceased patients that suffered from the disease. Tracking it
while they are alive, has been harder. A team from Imperial College
Healthcare detected the substance in live patients for the first
time in the UK, only in
December 2013
. At this point, the disease has also progressed
to its later stages, though the plaque spends years
accumulating.

It’s also possible to carry out a PET imaging scan, using a
chemical that will bind to the a protein in the plaque to highlight
it, and a cerebrospinal fluid test that identifies amyloid. Both
are expensive and not a common form of diagnosis in most
places.

Four teams are hoping to tackle the predicament this has left us
in, in two ways:

The eye test

A team from the Commonwealth Scientific and Industrial Research
Organisation in Australia and one from private company Cognoptix
have revealed their technologies for detecting beta-amyloid plaque
in the retina.

The Australian team carried out a trial on 200 volunteers using
a retinal amyloid imaging (RAI) system developed by
California-based NeuroVision Imaging. It works by using a substance
containing curcumin (found in turmeric) to bind to the plaques and
turn them fluorescent for the purposes of the imaging test. All
participants also underwent a PET scan to verify the results. Of a
group of 40 (the rest of the 160 patient results are pending) every
individual with Alzheimer’s had the disease accurately diagnosed
using the eye test, while 80.6 percent of those without Alzheimer’s
had an accurate test. The tests also showed that the plaque built
up by 3.5 percent over a 3.5-month period.

Keith Black, professor and chair of Cedars-Sinai’s Department of
Neurosurgery, which developed the NeuroVision Imaging system,
explained that this has been made possible because the retina is
part of the central nervous system. “A few years ago, we discovered
at Cedars-Sinai that the plaques associated with Alzheimer’s
disease occur not only in the brain but also in the retina. By
‘staining’ the plaque with curcumin, a component of the common
spice turmeric, we could detect it in the retina even before it
began to accumulate in the brain.”

The team believes it could be administered regularly, to test
how a patient is responding to treatment.

Cognoptix, conversely, uses an ointment that again binds to the
plaque, turning it fluorescent before a laser scanner picks it up.
Twenty individuals thought to have Alzheimer’s and 20 healthy
individuals of the same age were tested. Again, all also underwent
a PET scan to verify the results. This time around, those with the
disease tested positive in 85 percent of cases, while those without
Alzheimer’s tested negative 95 percent of the time. 

The sniff test

A team from Harvard Medical School and Harvard School of Public
Health studied 215 elderly patients enrolled in an ageing study at
the university. They administered a smell test devised by the
University of Pennsylvania, cognitive tests, amyloid deposit tests
and also measured the size of the entorhinal cortex and the
hippocampus in the temporal lobes, both associated with memory
functions. They found these brain structures were markedly smaller
than normal in those who had poorer memories and did poorly on the
smell test. They also identified a group that had elevated levels
of the amyloid protein in the brain, and simultaneously had a far
thinner entorhinal cortex — this group had a far worse memory for
smells.

Matthew Growdon, who helped head up the Harvard story, said the
test hold promise. However, he added: “Our findings are promising
but must be interpreted with caution. These results reflect a
snapshot in time; research conducted over time will give us a
better idea of the utility of olfactory testing for early detection
of Alzheimer’s.”

A second team from Columbia University Medical Centre carried
out a massive test on 1,037 individuals without symptoms, from 2004
up until 2010. The Pennsylvannia test had again been administered,
and in 757 individuals a poor score was linked with a progression
to dementia and Alzheimer’s. For every point a person scored lower
on the test, their chance of Alzheimer’s increased by 10 percent,
the team calculated.

“If further large-scale studies reproduce these results, a
relatively inexpensive test such as odour identification may be
able to identify subjects at increased risk of dementia and
Alzheimer’s disease at a very early stage, and may be useful in
identifying people at increased risk of cognitive decline more
broadly,” said Davangere Devanand, Professor of Psychiatry at the
Centre.

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Source: wired.co.uk
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