Mayo Clinic researchers explain Alzheimer's 'treatment window'
Researchers at Mayo Clinic continue to unravel dementia-related puzzles, taking steps toward one day effectively treating Alzheimer's and other memory diseases.
The key, say scientists at Mayo in Rochester, seems to lie in a "treatment window" of more than a decade, from the time the disease takes root in the brain until the moment a person first shows outward symptoms.
"Our study suggests that plaques in the brain that are linked to a decline in memory and thinking abilities, called beta amyloid, take about 15 years to build up and then plateau," Mayo radiologist Dr. Clifford Jack was quoted as saying in February, when the "treatment window" first was announced.
The study reviewed brain scans of plaque buildup in 260 people, age 70 to 92.
Treatment of plaque buildup after it plateaus might not be effective, Jack said in an interview earlier this year.
But earlier than that, during the treatment window, it could be. That means early diagnosis will provide more time to treat the disease once an effective treatment is found.
Thus, the key to future Alzheimer's treatment hinges on two developments: developing an effective treatment, and developing methods to predict the disease or diagnose it earlier.
"In individual subjects, the amyloid will, obviously, start at low levels," Jack said. "At some point, maybe late 50s, 60s, 70s — it varies in the individual — the rate will accelerate. And then the rate will decline, and the rate will reach a plateau once a high level of amyloid is reached in the brain."
By the time a person develops symptoms, deposition of plaques has likely already plateaued, he said.
"If you're going to treat amyloid, that has to be done very early in the disease," Jack said.
From the very earliest moment amyloid plaques are detectible to the time when Alzheimer's symptoms present themselves takes, on average, 15 years, he said. It's not until symptoms appear that plaque-prevention treatment loses effectiveness.
"It's remarkable if you think about it, because this is one of the cardinal pathologies of the disease, and what we're saying is it's actually played itself out. It's plateaued," Jack said.
Researchers at Mayo and elsewhere are seeking ways to detect Alzheimer's plaques very early in development, like a PSA test is used to suggest prostate cancer.Already, tests can show whether a person has abnormal plaque levels.
So who should get screened?
"The answer to that question is going to change the minute an intervention that targets amyloid is approved by the FDA," Jack said. Currently, Alzheimer's drugs treat symptoms, not the disease itself, he said.
So the only reason to get a plaque scan is to clarify disease status. Scans are not covered by insurance, Medicare or Medicaid because a scan will not change treatment.
Every amyloid-prevention study so far has failed, Jack says. But he believes that's because the tests studied have involved participants who already have dementia — in other words, for whom it's too late.
"You need to treat people that are normal," he said, "so you have a treatment arm and a placebo arm. You need to demonstrate that someone who otherwise would have gotten cognitive symptoms, with treatment, didn't — compared to people on the placebo arm who did," Jack said.
That will require enrolling "massive numbers of people" and following them for many, many years (perhaps from mid-life to late-life). Thus, cost and time are a barrier.
Jack's laboratory does MRIs for three 2013 plaque-prevention clinical trials. Two are enrolling people with very-uncommon mutations that produce 100 percent certainty of Alzheimer's developing generally early in life (and typically at about the same age as the affected parent).
Drugs in those studies have been shown to remove plaque. A third study examines elderly participants who have documented plaque without symptoms. About 30 percent of cognitively unaffected elderly people screened will have evidence of plaques.