New Alzheimer’s Guidelines: Will They Help Doctors Spot the Disease Earlier?

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For the first time in nearly three decades, experts have created a set of guidelines to better diagnose Alzheimer’s disease in the clinic. The advice also helps doctors identify the earliest signs of the degenerative condition, even before symptoms of memory loss begin. The hope is that they can help patients prepare early, and eventually treat, the disease.

I first wrote about these guidelines when the Alzheimer’s Association and the National Institute on Aging released a draft version in June 2010, so that researchers could review and comment on them. Not much has changed in the final version, but here’s a breakdown of how they will be applied.

Currently, Alzheimer’s disease can be definitively diagnosed only at autopsy, when pathologists can confirm the presence of protein plaques and tangles in the brain of a patient who had shown signs of memory loss and cognitive deficits. The new guidelines tease apart three different stages of the disease that are meant to help doctors better identify affected patients while they are alive. The phases also reflect the latest research, which suggests that Alzheimer’s develops in the brain over a long period of time — perhaps years or even decades before the first cognitive deficits are noticeable.

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The first stage, known as preclinical Alzheimer’s disease, includes those who are on the road to the neurodegenerative decline typical of the condition. These patients have no signs of any problems yet — they have no difficulty with memory or recall, and remain mentally intact — but in their brains, the protein amyloid is starting to build up. Scientists are developing ways to detect this subtle accumulation, just as blood tests pick up rising cholesterol levels that can contribute to heart disease, and imaging screens identify the smallest lesions that will become cancerous tumors.

The guidelines suggest ways that blood tests sensitive enough to pick up abnormal levels of amyloid, as well as tests of spinal fluid for the protein, might be used at this stage to identify those who might be at greater risk of developing Alzheimer’s. The experts creating these guidelines stress that the tests should be used only in research studies at this point, since they have yet to be validated. But doctors need to start studying them, they said, and should learn to familiarize themselves with how they might work.

The next phase is called pre-dementia, and encompasses patients who might be showing the first signs of memory lapses, changes in learning or attention, and other deficits in thinking. Otherwise known as mild cognitive impairment (MCI), these symptoms may be noticeable to both the patient and her family and friends, and while obvious, they may not be severe enough yet to cause any problems with daily activities. A subset of those with MCI go on to develop Alzheimer’s, and the guidelines specify four levels of the condition that can help doctors distinguish which cases are more likely to progress to Alzheimer’s and which are not.

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Also at this stage, newer techniques such as brain imaging studies are hinting that it may be possible to separate Alzheimer’s MCI from other types of dementia, but these are also still in the research stages and not ready for use in diagnosing patients in the clinic.

Finally, the guidelines specify the criteria for the third stage, which includes patients with dementia due to Alzheimer’s disease; these patients have cognitive deficits that impair a person’s ability to function in his daily life. In addition, this stage would include people with genetic mutations linked to the disease, which are responsible for both the early onset condition that runs in families as well as the more common dementia that progresses later in life.

Even for patients with dementia, the guidelines suggest the potential use of blood or imaging tests that could further distinguish abnormal deficits associated with Alzheimer’s from the more normal mental decline typical of aging.

The idea behind the guidelines is to make it easier for non-specialists — physicians without access to sophisticated brain imaging instruments or the latest assays for blood or spinal fluid tests — to distinguish the Alzheimer’s patient from others suffering from dementia. That way, say experts, these patients could become part of research studies in which newer methods for diagnosing the disease can be tested and validated. Such participants would also be eligible for testing new treatments that might stop or reverse the neurodegenerative disease, and if those prove successful, would help turn the tide on the flood of cases that are expected in the coming years as the baby boom population ages.

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The guidelines may not make a significant difference in the everyday care of patients today, but they could lay the foundation for a fundamental shift in understanding and treating the disease tomorrow.