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Finding Alzheimer's Before It Strikes

Getting disoriented in a virtual treasure hunt could be an early warning sign.
(Photo: hapal/Flickr)

(Photo: hapal/Flickr)

Although researchers don't know how to treat Alzheimer's, there's still plenty of reason to try catching the disease early. If nothing else, doing so can help families plan for an uncertain future. Now, researchers report, there may be a new way to identify those most at risk long before the first symptoms emerge: using a mix of brain scans and virtual treasure hunts.

"Late-onset AD [Alzheimer's Disease] is the most common form of dementia and one of the most challenging diseases of modern society," writes a German and Dutch team of neuroscientists led by Lukas Kunz, a medical student at the University of Bonn. Yet there remains no known cure, the team writes, "presumably because they start too late." Catching the disease early might help researchers study its progress and test out potential treatments, and could help patients better prepare for the difficult road ahead. But so far, the only tests in wide use are designed to catch memory problems that could prefigure Alzheimer's onset.

The earliest signs of Alzheimer's might show up not as memory problems, but rather as difficulties with navigation.

Kunz and his fellow researchers thought there could be another way to test for the disease, based on where in the brain Alzheimer's begins—namely, the entorhinal cortex, a region of the brain dense with grid neurons. Those neurons (whose discoverers shared the 2014 Nobel Prize for their efforts) generate an internal coordinate system that allows us to orient ourselves even in relatively featureless landscapes. Therefore, Kunz and his team reasoned, the earliest signs of Alzheimer's might show up not as memory problems, but rather as difficulties with navigation. Furthermore, those navigational troubles ought to show up on brain scans as signals in the entorhinal cortex.

To try out that idea, the researchers first tested students—almost all in their late teens and early 20s—at the University of Bonn for a gene variant called APOE E4, which is associated with an increased risk of Alzheimer's. Then, they had 38 students with that variant and 37 others lay down inside an MRI machine, where they were shown a computer-generated mountain "arena," a large circular area bounded by rocky cliffs. Each student moved around the arena in search of everyday objects such as baby bottles or eggplants. After they found each object, participants were supposed to return to their original starting points.

Students at increased genetic risk for Alzheimer's, the team found, did two things different from others. First, they were, on average, slightly more likely to spend time searching the periphery, rather than the center, of the arena. Second, they were less likely to align their movements with their own internal coordinate systems, an observation which showed up on the brain scans as reduced activity inside the entorhinal cortex.

That's still a long way from a clinical test, in part because the results only connect navigational abnormalities to the E4 gene variant, rather than directly to Alzheimer's. Still, the findings could point the way toward a deeper understanding of Alzheimer's and—maybe someday—new treatments for the debilitating disease.

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