U.S. Autopsy Guidelines Revised for Alzheimer's

For many years, an autopsy done by a pathologist was considered the best way to confirm the presence of Alzheimer's disease.

But new guidelines proposed on Sunday by the U.S. National Institute on Aging and the Alzheimer's Association seek to distinguish between memory changes or dementia diagnosed by doctors when people are alive, and the changes pathologists can see in an autopsy.

The proposed guidelines will offer additional information about the disease that will help as scientists develop tests that measure biological changes in the brain, blood or spinal fluid to diagnose Alzheimer's at an earlier stage.

Several companies, including Eli Lilly and Co, Bayer and General Electric Co, are working on compounds to identify Alzheimer's-related brain changes on positron emission tomography scans.

Many other companies and researchers are working on other types of biomarkers as well.
"Someday biomarkers are probably going to replace pathology," Dr. Creighton Phelps of the

National Institute on Aging's division of neuroscience, said in an interview at the Alzheimer's Association International Conference in Paris.

Pathologists now look in the brain for clumps of a protein called beta amyloid and a protein called tau to diagnose Alzheimer's disease.

But studies have shown that people can die with lots of plaques and tangles in their brain and still have normal cognitive function.

"We know people die with Alzheimer's changes in the brain but they had no dementia," Phelps said.

According to the proposed guidelines, patients who have memory problems caused by the disease will be diagnosed with Alzheimer's dementia, or in milder cases, mild cognitive impairment (MCI) due to Alzheimer's dementia.

The term Alzheimer's disease will be used to refer to the underlying changes in the pathology, Phelps said.

"Classically, it's all been one big pool but they are not equivalent," he said. "You might have something on a slide that doesn't match what the person was like in life."

Phelps said dementia can be caused by many diseases, including vascular disease, so it is important to be clear about what is causing the problem.

The proposed guidelines offer much more detail about how to test people's brains at autopsy, specifying tests that should be done and asking pathologists to quantify the amount of plaque in the brain.

Bill Thies of the Alzheimer's Association said knowing the location of the plaques in a person's brain may provide clues about why some people develop dementia and others do not.

If these protein deposits are clustered in memory centers of the brain, that could cause more problems than if they are in other parts, for example.

Earlier this year, the NIA, part of the National Institutes of Health, and the Alzheimer's Association issued new diagnostic criteria to help doctors better classify patients who are tested for signs of dementia.

The proposed pathology guidelines, which are part of that process, will be available for public comment until September 1. Phelps said he hopes final guidelines will published in January 2012.