Alzheimer’s research needs an overhaul, scientists say

By Kay Lazar, Globe Staff

People who have no symptoms of Alzheimer’s disease but who have an abnormal protein believed to be a hallmark of the illness should be enrolled in clinical trials to test whether drugs can head off the disease, according to a team of researchers led by a scientist at Boston’s Brigham and Women’s Hospital.

There is no known cure for Alzheimer’s disease, and recent drug trials have produced disappointing results.

But in an article published today, the researchers say that may be because the drugs are now tested only in people whose Alzheimer’s is too advanced. The lead author, Brigham Alzheimer’s specialist Dr. Reisa Sperling, said she plans to apply for a federal grant next year to study such drugs in patients with the abnormal protein in their brains who do not yet have Alzheimer’s symptoms.

More than 1 out of every 10 people over the age of 65 has Alzheimer’s, and given the approaching tsunami of aging baby boomers, the United States is facing an Alzheimer’s epidemic, the researchers say.

“We are facing 10,000 people a day turning 65,” said Sperling, lead author of the article today in Science Translational Medicine. “We have to do something to prevent Alzheimer’s, or we are sunk.”

Just as patients with high cholesterol are routinely given medications to lower their levels before they have a heart attack, patients with large amounts of an abnormal protein, known as beta amyloid, in their brains should be given medicines to clear those proteins long before they show memory loss or other early symptoms of Alzheimer’s, the researchers said.

The argument makes sense, said Maria Carrillo, senior director of medical and scientific relations at the Alzheimer’s Association.

“We can learn from other fields that have moved toward affecting the disease course when they treat it earlier in the process,” Carrillo said. “Similarly in Alzheimer’s, if you catch it preclinically, you may be able to delay or stop symptoms from progressing.”

A number of studies have indicated that the accumulation of amyloid plaques may be damaging a person’s brain at least a decade before Alzheimer’s symptoms first appear, although it’s not yet clear whether the protein buildup is a cause of the disease or an early symptom. Scientists believe that more than 50 percent of certain critical brain cells are already lost by the time a patient displays even mild cognitive impairment.

So why are scientists still testing potential Alzheimer’s medications so late in the disease process?

Because there is not a reliable test, brain imaging or other method to accurately detect the disease before symptoms appear, Carrillo said. So they have resorted to testing medications in patients who already show some decline.

Federal regulators are reviewing a brain imaging product for early detection that could be approved as early as next year, she said.

Though some experimental medications have shown an ability to reduce the amount of amyloid in the brains of patients who already are impaired, that has not translated into improvement in symptoms.

Sperling said researchers face several challenges before they can test drugs on people without Alzheimer’s symptoms.

Perhaps the “most daunting,” she said, is the need to develop an accurate measure of when someone who is not showing any obvious signs of Alzheimer’s “tips from cognitively normal to subtly abnormal.” Researchers believe that change can happen years before a formal diangosis of mild impairment is typically made.

Sperling is hoping to begin a three-year study of an amyloid-clearing medication next year on as many as 1,000 people, 70 years old and older, whose brains show an accumulation of amyloid plaques but who don’t appear to be impaired. She said she will seek funding for the study from the National Institutes of Health.

It would be the first known study of an anti-amyloid drug on people without Alzheimer’s symptoms.

“We have to shift the paradigm,” Sperling said. “Clearly what we are doing now is not working fast enough.”