Alzheimer's begins long before symptoms of memory loss appear, study suggests

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Alzheimer’s disease begins destroying the brain years before mental deterioration is detected, a new study suggests. This finding means there could be twice the number of people with the neurodegenerative disease in the United States — and worldwide — as currently believed.

Cognitively normal individuals who had elevated levels of a toxic brain protein called amyloid experienced more rapid declines in thinking than those with normal levels. The 445 subjects were followed for as long as 10 years after their assessment to detect any changes. The median time was 3.1 years, and the subjects’ average age was 74.

The study adds to evidence that Alzheimer’s actually begins years before symptoms appear, said Dr. Paul Aisen, senior author of the study. Aisen directs the University of Southern California’s Alzheimer's Therapeutic Research Institute, located in San Diego.

Published in the Journal of the American Medical Association, the study can be found at Aisen is the senior author; Michael Donohue, also of ATRI, is first author.

“I think this is important confirmation of the hypothesis that has been guiding our work,” Aisen said.

The finding has vast implications for health care, according to an accompanying JAMA editorial. It poses unsettling questions about how to tell people they may be on the path to Alzheimer’s well before any impairment occurs.

And the very definition of the disease should be changed to reflect that people can live with Alzheimer’s for a long time without cognitive impairment, the editorial says.

The study also points a way to beginning treatment far earlier than is done now, early enough to stop the disease before irreversible brain damage is done, Aisen said.

“My vision of the future is that many people will have screening for amyloid accumulation as they get older,” Aisen said.

“Some may decide not to have screening, just as some don't have a colonoscopy for colon cancer or don't check their cholesterol for cardiovascular disease. But I think that screening for amyloid abnormalities is going to be part of health care, when we have effective therapy for Alzheimer’s disease.”

The screening will probably start in middle age, Aisen said. People who show signs of amyloid accumulation can then be offered access to experimental drugs aimed at stopping the process.

Significant progress

The study, and its use of the amyloid biomarker, significantly expands knowledge about how Alzheimer’s begins, said James Brewer, M.D., Ph.D., a University of California San Diego neuroscientist who is also interim director of the Shiley-Marcos Alzheimer's Disease Research Center.

“It’s an exciting time in Alzheimer's research to finally have these biomarkers that can work inside the living brain, because it's going to allow us to better understand this disease in the living human rather than relying on animal models or other potentially misleading approaches,” Brewer said.

Brewer uses MRI technology to study memory, both in healthy people and those with Alzheimer’s.

Alzheimer’s disease is today diagnosed with cognitive tests, aided in recent years by detection of amyloid, which has long been implicated in Alzheimer’s, in living patients.

Previously, Alzheimer’s could only be definitively diagnosed by autopsy, when the pathological changes characteristic of Alzheimer’s could be detected. Amyloid and another abnormal protein, tau, are believed to start the process, causing neurons to become diseased and eventually die.

That has changed with the development of imaging technology to non-invasively detect amyloid and tau in the brains of living people, coupled with more traditional imaging tools.

This work has been coordinated by the Alzheimer’s Disease Neuroimaging Initiative at USC, which seeks to find biomarkers associated with Alzheimer’s.


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