- Robert Preidt
- Posted April 13, 2020
Brain Plaques Signal Alzheimer's Even Before Other Symptoms Emerge: Study
Even before symptoms develop, the brains of people with early Alzheimer's disease have high levels of amyloid protein plaques, a new study reveals.
Those levels in older adults with no dementia symptoms are associated with a family history of disease, lower scores on thinking/memory tests, and declines in daily mental function.
The first findings from the so-called A4 study funded by the U.S. National Institute on Aging (NIA) were published recently in the journal JAMA Neurology. A4 stands for Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease.
The study -- due for completion in late 2022 -- is an ongoing trial that was launched in 2014. It's investigating whether the drug solanezumab can slow mental decline associated with elevated amyloids if people start taking it before Alzheimer's symptoms emerge.
Amyloid, a hallmark of Alzheimer's, has been the target of experimental treatments in clinical trials involving people who already have symptoms of the disease.
"A major issue for amyloid-targeting Alzheimer's disease clinical trials, and one that is being addressed with the A4 study, is that previous trials may have been intervening too late in the disease process to be effective," said NIA director Dr. Richard Hodes.
"A4 is pioneering in the field because it targets amyloid accumulation in older adults at risk for developing dementia before the onset of symptoms," he noted in a NIA news release.
The researchers used amyloid positron emission tomography (PET) imaging to screen nearly 4,500 older adults for the study. The investigators identified and enrolled more than 1,300 with high amyloid levels in the brain, but no Alzheimer's symptoms.
The study was the first to use PET to identify people with high levels of amyloid but no signs of mental ("cognitive") decline, according to Laurie Ryan, chief of the NIA's Dementias of Aging branch.
"Before the availability of amyloid PET, other amyloid-targeting clinical trials may have been testing therapies in some people who didn't have amyloid," she said in the news release.
Lead author Dr. Reisa Sperling, of the neurology department at Brigham and Women's Hospital in Boston, said screening data for all those who had PET scans is available to other researchers. It may help improve screening and enrollment in other trials designed to prevent Alzheimer's in people without symptoms, she said.
According to Ryan, "A4 demonstrates that prevention trials can enroll high-risk individuals -- people with biomarkers for Alzheimer's who are cognitively normal. Ultimately, precision medicine approaches will be essential."
She predicted that Alzheimer's disease will never have a "one-size-fits-all" treatment. "We're likely to need different treatments, even combinations of therapies, for different individuals based on their risk factors," Ryan explained.
The Alzheimer's Association has more on Alzheimer's disease.
SOURCE: U.S. National Institute on Aging, news release, April 6, 2020