Unique graphic
characters called Greebles may prove to be valuable tools in detecting signs of
Alzheimer's disease decades before symptoms become apparent, according the
recent study of University of Louisville.
Which Greeble is
different?
In an article published online last week in Journal
of Alzheimer's Disease, Emily Mason, Ph.D., a postdoctoral associate in the
Department of Neurological Surgery at the University of Louisville, reported
research showing that cognitively normal people who have a genetic
predisposition for Alzheimer's disease (AD) have more difficulty distinguishing
among novel figures called Greebles than individuals without genetic
predisposition.
Those unable to tell which character is the odd one out
could well be at risk of the devastating illness.
Known as Greebles, the little purple characters have been
designed by scientists in their ongoing quest for a cure. A study found those
at genetic risk of the disease struggle to distinguish a subtle difference in
one of the images. But they may be unaware of their likelihood as they are
still able to detect minor changes in people's faces, objects and scenes.
Alzheimer's disease (AD) is a progressive, irreversible
neurodegenerative disease characterized by declining memory, cognition and
behavior. AD is the most prevalent form of dementia, affecting an estimated 5.5
million individuals in the United States and accounting for 60 to 80 percent of
dementia cases. The ability to detect the disease earlier may allow researchers
to develop treatments to combat the disease.
"Right now, by the time we can detect the disease,
it would be very difficult to restore function because so much damage has been
done to the brain," Mason said. "We want to be able to look at really
early, really subtle changes that are going on in the brain. One way we can do
that is with cognitive testing that is directed at a very specific area of the
brain."
AD is characterized by the presence of beta amyloid
plaques and tau neurofibrillary tangles in the brain. Tau tangles predictably
develop first in the perirhinal and entorhinal cortices of the brain, areas
that play a role in visual recognition and memory. Mason and her colleagues
developed cognitive tests designed to detect subtle deficiencies in these
cognitive functions. They hoped to determine whether changes in these functions
would indicate the presence of tau tangles before they could be detected
through imaging or general cognitive testing.
Working in her previous position at Vanderbilt
University, Mason identified test subjects age 40-60 who were considered
at-risk for AD due to having at least one biological parent diagnosed with the
disease. She also tested a control group of individuals in the same age range
whose immediate family history did not include AD.
The subjects completed a series of
"odd-man-out" tasks in which they were shown sets of four images
depicting real-world objects, human faces, scenes and Greebles in which one
image was slightly different than the other three. The subjects were asked to
identify the image that was different.
The at-risk and control groups performed at similar
levels for the objects, faces and scenes. For the Greebles, however, the
at-risk group scored lower in their ability to identify differences in the
images. Individuals in the at-risk group correctly identified the distinct
Greeble 78 percent of the time, whereas the control group correctly identified
the odd Greeble 87 percent of the time.
"Most people have never seen a Greeble and Greebles
are highly similar, so they are by far the toughest objects to differentiate,"
Mason said. "What we found is that using this task, we were able to find a
significant difference between the at-risk group and the control group. Both
groups did get better with practice, but the at-risk group lagged behind the control
group throughout the process."
Mason would like to see further research to determine
whether the individuals who performed poorly on the test actually developed AD
in the future.
"The best thing we could do is have people take this
test in their 40s and 50s, and track them for the next 10 or 20 years to see
who eventually develops the disease and who doesn't," Mason said.
In recent years, a great deal of research has focused on
identifying early biomarkers of Alzheimer's disease. However, not everyone who
has an individual biomarker ultimately develops the disease. Brandon Ally,
Ph.D., assistant professor of neurological surgery at UofL and senior author of
the publication, said the tests with Greebles can provide a cost-effective way
to identify individuals who may be in the early stages of AD, as well as a tool
for following those individuals over time.
"We are not proposing that the identification of
novel objects such as Greebles is a definitive marker of the disease, but when
paired with some of the novel biomarkers and a solid clinical history, it may
improve our diagnostic acumen in early high-risk individuals," Ally said.
"As prevention methods, vaccines or disease modifying drugs become
available, markers like novel object detection may help to identify the high
priority candidates."
Robert P. Friedland, M.D., professor and Mason and Mary
Rudd Endowed Chair in Neurology at UofL, has studied clinical and biological
issues in Alzheimer's disease and related disorders for 35 years. He believes
that early detection will enhance the ability of patients and physicians to
employ lifestyle and therapeutic interventions.
"This work shows that the effects of Alzheimer's
disease on cognition can be measured decades before the onset of
dementia," Friedland said. "The fact that the disease takes so long
to develop provides us with an opportunity to slow its progression through
attention to the many factors that are linked to the disease, such as a
sedentary lifestyle, a high fat diet, obesity, head injury, smoking, and a lack
of mental and social engagement."
The study found: “In conclusion, we have demonstrated
that middle-aged subjects at risk for developing Alzheimer’s disease
demonstrate a clear difference in perceptual processing decades before the
expected onset of the disease.
“This difference is most apparent in novel stimuli with a
high degree of feature ambiguity.
“This task may have clinical utility in identifying
subjects with early Alzheimer’s disease pathology decades before a diagnosis.”
Experts found the results were not as marked as tests
looking at the face, objects and scenes.
So, which is the odd one out?
ANSWER: Greeble No.
4 is different (on the top picture) and No. 3 (on the bottom picture).
The fourth Greeble
in the first picture is the odd one out. The character has a bigger, pointier
and wider horns on it’s head and it’s arm also sticks out more than the other
three Greebles. In the second picture, the third greeble is the odd one out.
Sources and
Additional Information: https://www.sciencedaily.com/releases/2017/04/170411085745.htm
