Among the many difficult features of Alzheimer's is that doctors can never really say with certainty which patients who show signs of memory loss will go on to develop the neurodegenerative disorder.
That's because not all people who show lapses in memory necessarily have Alzheimer's. Even people who have higher levels of the brain-clogging protein amyloid, the hallmark of the disease, don't necessarily develop it.
But in the latest study on screening patients for early biomarkers of Alzheimer's, an international group of scientists reports that a combination of tests could predict with about 80% those who will develop the disease.
The researchers focused on 58 patients with mild cognitive impairment (MCI), a condition that includes memory lapses and periods of confusion that are more severe than the normal senior moments that come with aging, but not severe enough to qualify as dementia. About 15% of patients who have MCI go on to develop Alzheimer's. The question is, which ones?
When the team looked at the levels of an early form of amyloid in the spinal fluid of participants, they found that MCI patients with higher levels of the protein's precursor were more likely to get Alzheimer's three years later. Doctors currently test for a later form of amyloid protein, which may help them distinguish Alzheimer's from other possible causes of memory loss, but which the authors believe may appear too late in the disease process to be of use in predicting which patients will transition from MCI to Alzheimer's.
When the scientists combined the reading of amyloid precursor in the spinal fluid with tests for another protein called tau, which is made when nerve cells start to break down, along with the patient's age, they were able to predict with 80% accuracy which patients with MCI would experience a decline in their condition toward Alzheimer's.
"We might have found something that could really provide significant health benefit for patients from a medical and not just research perspective," says co-author Robert Perneczky, in the department of psychiatry and psychotherapy at the Technical University of Munich.
Before doctors can start using the test, however, the findings will have to be confirmed in other populations of MCI patients. If they are validated, the screen might prove useful in helping those who are at higher risk of developing Alzheimer's to begin interventions that may delay progress of the disease. Although there aren't any effective treatments yet, studies have shown that keeping socially and physically active can slow down the cognitive decline that occurs once amyloid starts to interfere with normal nerve function in the brain. The study was published online in the journal Neurology.
Will They Help Doctors Spot the Disease Earlier?
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.
The first stage, known as preclinical Alzheimer's disease, includes those who areon 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.
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.
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. to learn about Alzheimer's disease,
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