Three stages of Alzheimer's
The new guidelines, published online in the Alzheimer's Association journalAlzheimer's & Dementia, separate Alzheimer's into three stages: "preclinical" Alzheimer's, a category defined only for research purposes that encompasses people with suggestive brain changes but no readily apparent symptoms; mild cognitive impairment, in which mental decline is noticeable and measurable but doesn't compromise independence; and Alzheimer's dementia, once the only form of the disease but now seen as a relatively late development.
Even in diagnosing people with frank dementia, the new guidelines confine the "biomarkers" tests to a strictly supporting role. "We're asking the physician, with the help of an informant — the patient and family — to make a judgment about whether dementia is occurring," said Guy M. McKhann, M.D., a neurologist at Johns Hopkins University School of Medicine and lead author of the guideline on dementia, in a media teleconference on the new guidelines. "Biomarkers can assist the diagnosis but are not essential."
For people with signs of mild cognitive impairment, a problem that may affect millions of people, guidelines writers said the goal was to create a clear framework for evaluating their condition. The guidelines provide methods for combining biomarker test results with observed symptoms to judge the likelihood that a patient's problem will progress to Alzheimer's dementia. But because of the uncertainties that still surround these tests, the experts propose their use mainly for research.
In a clinical setting, the workup for these patients would be very similar to what's been standard for the last decade, including tests to rule out non-Alzheimer's causes of mental impairment like a stroke or tumor. Currently there are no drugs approved to treat mild cognitive impairment. "For many people, it is important to know, to make plans, to discuss with their family the plans at a time when they are still able to make decisions for themselves," said Reisa Sperling, M.D., a neurologist at Harvard-affiliated Brigham and Women's Hospital in Boston and lead author of the guideline on presymptomatic Alzheimer's.
The guidelines propose even less of a role for the tests in diagnosing people with milder symptoms, except in clinical trials and other research settings.
Indeed, it's in research on the early pathology of Alzheimer's that the biomarker measurements will likely play a key role. These measurements can help scientists study just which biological changes predict progression to dementia, and help them tease out which factors actually cause the decline — and are therefore the best targets for experimental drugs.
"We believe that it's critically important, when we do have more effective drugs, to intervene as early as possible," said Marilyn Albert, director of the Johns Hopkins Alzheimer's Disease Research Center and lead author of the guideline on mild cognitive impairment.
Katharine Greider lives in New York and writes about health issues.
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