Study: A Blood Test May Predict Alzheimer’s

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John Livzey

Being diagnosed with Alzheimer’s disease, with its symptoms of memory loss and gradual slowing of brain functions, is challenging enough already. But for those who are affected, one of the condition’s most frustrating features is that the diagnosis itself isn’t definitive.

Because the cognitive decline of Alzheimer’s is nearly indistinguishable from other forms of dementia, only an autopsy that confirms the presence of protein plaques in the brain can conclusively diagnose the disease. But new research suggests that a blood test may soon be able to detect the degenerative neurological condition in living patients, well before the first symptoms emerge. (More on The Top 10 Medical Breakthroughs of 2010)

Led by Dr. Kristine, Yaffe, a professor of psychiatry at the University of California, San Francisco, a team of scientists studied a group of nearly 1,000 elderly adults for nine years. At the beginning of the study, the researchers took blood samples from the volunteers and measured levels of beta-amyloid, the protein that builds up in the brains of Alzheimer’s patients. Lower levels of amyloid in the blood presumably mean that more of the substance is being pulled out of circulation and deposited in the brain, where it is embedded between nerve cells and interferes with their normal function.

The elderly volunteers also completed a survey designed to test their cognitive functions, including memory and executive skills such as the ability to learn and retain new information.

After nine years, those with the lowest blood levels of beta-amyloid had dropped nearly twice the number of points on tests of cognitive function, compared with those who had higher levels of the protein. The level of amyloid in the blood, then, served as an indicator for future dementia risk.

“That was kind of exciting because it really looks like in our hands, the blood test did work, and we’re finding something really early — these people didn’t have dementia,” says Yaffe, whose study was published in the Journal of the American Medical Association (JAMA). (More on 5 New Rules for Good Health)

Testing for amyloid in the blood is only one of the many ways that experts are attempting to pick up the first signs of Alzheimer’s in living patients. Recent studies suggest that measuring amyloid in the spinal fluid, which has a more direct connection to the brain, may also be useful, as well as testing for other telltale proteins in the blood, known as biomarkers.

Even more encouraging for Yaffe was the second set of results from her experiment. Because Alzheimer’s researchers have also known that about 10% to 20% of patients who show evidence of amyloid on autopsy never exhibit signs of dementia or cognitive decline, Yaffe’s team thought the amyloid blood test could help explain this puzzling result. The most popular theory involves something called cognitive reserve: the idea is that people with more cognitive reserve are better able to compensate for the loss of nerves to amyloid, and can continue to function without signs of the disease even while it is ravaging their brain.

Cognitive reserve is still an undefined concept, but it is generally thought to involve everything from having a larger brain (and therefore more neural connections to keep it going) to maintaining cognitive networks by continually engaging them in learning new things.

To test this idea, Yaffe further stratified her study group by education and literacy, two commonly accepted ways of measuring cognitive reserve. It turned out that among those with low levels of amyloid in the blood, participants with higher education (more than a high school diploma) or at least a sixth-grade level of literacy were able to compensate, and experienced half the drop in cognitive function scores as those with lower education and less literacy.

That finding gives Yaffe hope that in coming years, early tests, including one for amyloid in the blood, could identify people at high risk of developing Alzheimer’s disease well before their first cognitive symptoms emerge. These individuals could then get a head start in using interventions that could treat or even prevent their disease. At the moment, no such medical therapies exist, but there is evidence that people with denser networks of friends and family, as well as those who engage their minds by learning new skills or a new language or by playing card games, are able to hold back mental decline better than those who do not take advantage of these opportunities. (More on 5 Ways to Get the Most Out of Health Reform)

“It does really look like the cognitive reserve hypothesis is important,” says Yaffe. “And [our results] also imply that it you have an elderly person and she gets a blood test and her amyloid is low, it may mean she is at risk of later cognitive problems. But this group might be one to target for more cognitive activity or other strategies that might prevent the decline.”

Yaffe acknowledges that an amyloid blood test won’t likely be the final word in an Alzheimer’s diagnosis. It’s still not entirely clear whether or how much of the protein in the blood signals disease — other conditions can result in amyloid in the blood as well, and it’s difficult to set threshold levels to identify when normal amounts of amyloid have increased enough to tip the scales to indicate a disease state.

Realistically, Yaffe says, doctors will probably rely on a combination of different measures to make the most accurate diagnosis they can. Also reporting Tuesday in JAMA, another research group showed success in using positron emission tomography, or PET scans, to detect amyloid, for example, and such tests combined with a blood test could eventually obviate the need to wait until autopsy to confirm an Alzheimer’s diagnosis. That means treatments, when they become available, can also be introduced earlier to control or hopefully even prevent the disease.

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