miércoles, 19 de enero de 2011

Two Tests Could Aid in Risk Assessment and Early Diagnosis of Alzheimer’s

Two Tests Could Aid in Risk Assessment and Early Diagnosis of Alzheimer’s

Researchers are reporting major advances toward resolving two underlying problems involving Alzheimer’s disease: How do you know if someone who is demented has it? And how can you screen the general population to see who is at risk?

New Old Age

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One study, reported in The New York Times in June, evaluated a new type of brain scan that can detect plaques that are uniquely characteristic of Alzheimer’s disease.
On Thursday, an advisory committee to the Food and Drug Administrationwhich requested the study, will review it and make a recommendation on whether to approve the test for marketing.
The second study asked whether a blood test could detect beta amyloid, the protein fragment that makes up Alzheimer’s plaque, and whether blood levels of beta amyloid were associated with a risk of memory problems. The answer was yes, but the test is not ready to be used for screening.
Both studies are to published in The Journal of the American Medical Association on Wednesday.
“These are two very important papers, and I don’t always say that,” said Neil S. Buckholtz, chief of the Dementias of Aging Branch of the National Institute on Aging.
The new brain scan involved a dye developed by Avid Radiopharmaceuticals, now owned by Eli Lilly. The dye attaches to plaque in patients’ brains, making it visible on PET scans.
The study by Avid involved 152 people nearing the end of life who agreed to have a brain scan and a brain autopsy after they died. The investigators wanted to know whether the scans would show the same plaques as the autopsies.
Twenty-nine of the patients in the study died and had brain autopsies. In 28 of them, the scan matched the autopsy results. Alzheimer’s had been diagnosed in half of the 29 patients; the others had received other diagnoses.
One subject who was thought to have had Alzheimer’s did not have plaques on the scans or on the autopsy — the diagnosis was incorrect. Two other patients with dementia turned out to have had Alzheimer’s although they had received diagnoses of other diseases.
The study also included 74 younger and healthier people who underwent the scans. They were not expected to have plaques, and in fact they did not.
If the F.D.A. approves the scan, medical experts said they would use it to help determine whether a patient with dementia had Alzheimer’s. If no plaques were found, they would have to consider other diagnoses.
The Avid scan will also be used — and is being used — by companies that are testing drugs to remove amyloid from the brain. The scans can show if the drugs are working. And a large study sponsored in part by the National Institute on Aging is scanning healthy people and following them to see if the scans predict the risk of developing Alzheimer’s disease.
The other study, on a blood test for Alzheimer’s, indicates that such a test may work. But researchers agree that it is not ready for clinical use.
The study, by Dr. Kristine Yaffe of the University of California, San Francisco, and the San Francisco Veterans Affairs Medical Center, included 997 subjects whose average age was 74 when the study began. They were followed for nine years and given memory tests and a blood test looking for beta amyloid.
Beta amyloid is in the brain and flows into the spinal fluid. From there, it can enter the bloodstream. When amyloid accumulates in plaque, its levels in spinal fluid go down. That indicates risk for Alzheimer’s disease.
Dr. Yaffe and her colleagues asked whether they could show similar Alzheimer’s risk by measuring beta amyloid levels in blood. It is difficult; amyloid levels in blood are much lower than in spinal fluid. And there appear to be other sources of amyloid in blood, confounding the test results.
“I was interested in the blood test because I think it’s been given a bit of a write-off,” Dr. Yaffe said. Some studies concluded that it worked, but just as many said that it did not. She wanted to try again with a large study following people for a long period and using a sensitive test for amyloid.
She divided the subjects into groups and found that those with the most amyloid had the lowest risk of a decline in their mental abilities, and those with the least had the greatest risk. But other factors also played a role. Low levels of the protein were not as useful in predicting mental decline in people who had more education and were more literate. People with a gene, APO e4, that is associated with an increased risk of Alzheimer’s, seemed to be at a greater risk of a mental decline even if their blood levels of amyloid were high.
That does not necessarily mean that the more people use their minds the more they will be protected from Alzheimer’s disease, researchers note. But, Dr. Yaffe said, that idea needs more study.
The test’s precision, said Dr. Clifford Jack of the Mayo Clinic, was “not crisp enough” to accurately predict whether an individual was likely to show an intellectual decline over the decade after the test was given.
Still, said Dr. Ronald C. Petersen, chairman of the medical and scientific advisory council of the Alzheimer’s Association, there is an increasing need for such a test. If treatments are developed to slow or stop the disease, it will be important to start them before irreversible damage is done.
Current tests of Alzheimer’s risk — spinal taps and MRI and PET scans — are not suitable to screen large numbers of people. “They are either expensive or invasive, or both,” Dr. Petersen said. “We need a cheap and safe population screening tool, like cholesterol for cardiology.”
A blood test could be ideal, and this study is an encouraging step forward, he said. The idea might be to screen with such a test and then follow up with those who test positive, giving them a PET scan, for example.
But, Dr. Petersen said, “this study is not sufficiently convincing that this is the answer.”

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