Looking Ahead: Tests might predict Alzheimer’s risk

In the century since German physician Alois Alzheimer first described the devastating brain disease that bears his name, the illness has resisted cure and its origins have remained elusive. Now, two teams of scientists report that years before symptoms appear, there are indications of who will develop the disease.

U.S. researchers show that brain scans can spot warning signs of cognitive decline, and a Swedish team reports that spinal fluid contains markers of Alzheimer’s risk. Such early diagnostic tests could increase the time available to treat the disease.

“Many people believe that we’re going to have treatments [for Alzheimer’s] in 5 years,” says William Jagust, a physician and neuroscientist at the University of California, Berkeley. “And there’s virtual unanimity of opinion that the drugs will be far more effective if given to people before they develop symptoms.”

Jagust and his colleagues performed positron emission-tomography scans and magnetic resonance imaging on 60 volunteers who had no cognitive impairments and were ages 60 to 100. Annual tests of cognition over the next 4 years showed memory declines or other mental losses in six of the participants. Scans of those participants taken at the start of the study revealed that specific areas of the brain had shrunk or become less active. Brain scans of the other 54 participants showed less shrinkage and more activity in these areas.

The locations affected in the six participants with mental declines matched spots that autopsies commonly reveal as damaged in Alzheimer’s patients. “It’s guilt by association,” Jagust says. “We think it’s very suspicious” that the same regions are damaged in both groups.

The report will appear in the April Annals of Neurology.

“This is a unique study,” says neurologist Charles DeCarli of the University of California, Davis. “These are important pieces of information to have available. Their true impact will be seen when we have therapies” for Alzheimer’s disease, he says.

A team of Swedish researchers took a different approach. They performed spinal taps on 137 people ages 50 to 86 who had mild cognitive impairments—beyond the normal challenges that come with aging—that affected their language, memory, or critical thinking. The team tested the spinal fluid for concentrations of tau protein and beta-amyloid, two substances implicated in Alzheimer’s disease.

Over 4 years, 57 of the people developed Alzheimer’s disease. Those whose spinal fluid at the start had abnormally high tau protein and low beta-amyloid concentrations were nearly 18 times as likely to develop Alzheimer’s disease as were people with normal concentrations, says physician Kaj Blennow of Gothenburg University in Sweden. Almost all the people in the high tau–low beta-amyloid group were diagnosed with Alzheimer’s disease during the study.

The report will appear in the March Lancet Neurology.

The new work shows that “even in the early stages, you can find evidence that the disease is there or is coming,” says Steven T. DeKosky, a neurologist at the University of Pittsburgh.

Drugs currently available for Alzheimer’s disease can ease symptoms but don’t slow disease progression. That’s likely to change, DeCarli says. “It’s my understanding that every major pharmaceutical company is working on an Alzheimer’s drug or has one in the pipeline,” he says.

When drugs become available to fight Alzheimer’s, “there will be a very high demand for diagnostic methods,” Blennow predicts.