ANN ARBOR, MI – Even though Alzheimer's disease takes a terrible toll on the memories and lives of millions of adults each year, doctors often face great uncertainty when trying to diagnose it in living people. Several other diseases can mimic the symptoms of Alzheimer's disease, and only an autopsy can confirm a diagnosis for certain.
The lack of a definitive Alzheimer's test didn't matter so much in the past, but in recent years new drugs and therapies have been shown to slow the spiral of memory loss and behavior changes that Alzheimer's patients face. A good new diagnostic test could help patients get help early -- and make the most of their remaining years.
That's why University of Michigan Health System researchers and others are so excited about a kind of medical imaging that they think can tell Alzheimer's disease apart from other disorders. By looking at the brain with a special camera, they hope to give patients a more definitive diagnosis while they can still do something about it.
The "camera" in question is really a machine called a PET scanner; PET stands for positron emission tomography. Doctors already use PET to find cancer and heart problems, but a team led by U-M researchers recently released the first conclusive study showing it could be used to tell Alzheimer's disease from other disorders.
"PET scanning is a way to look at the brain in people who are living and dealing with their disease," says Norman Foster, M.D., the U-M neurologist leading the research team. "The PET machine looks very much like an MRI or CT scanner, but it's different because it can show not just what the brain looks like inside the head, but how active different parts of the brain are and how they're reacting to the disease."
This brain activity -- or lack of it -- is what matters in Alzheimer's disease, adds Foster, who directs the Cognitive Disorders Clinic at the U-M Geriatrics Center and is a professor in the U-M Department of Neurology and associate director of the Michigan Alzheimer's Disease Research Center.
In Alzheimer's patients, many of the brain's nerve fibers are lost, and an abnormal buildup of protein damages nerve cells. Though the causes are mostly unknown, save for a suspected genetic link in some cases, the effects are all too apparent. Patients who start out with absentmindedness and mild memory loss worsen to become restless, moody, anxious, and confused, with increasing memory loss. In the final stages, patients often lose the ability to talk to others or care for themselves.
Initial results were presented recently at the International Conference on Alzheimer's Disease and Related Disorders. Based on the U-M-led study, and other evidence, Foster feels that earlier diagnosis with PET could become a common practice within a few years, and help guide treatment.
Experts estimate that 3 million to 4 million Americans have some form of Alzheimer's disease. But the exact number is unknown due to difficulty in diagnosis, especially in the early stages.
Doctors often use checklists of symptoms, and other behavioral assessment tools, to help them try to detect Alzheimer's. But such methods can produce major variations in medical opinion about a single patient. Adding to the confusion are a group of related disorders -- all called dementias -- which all share common symptoms of declining intellectual abilities.
"Alzheimer's disease can be mimicked by many other similar illnesses. And in some cases, memory loss isn't the first symptom – it could be behavioral or language changes, or difficulty with everyday activities," Foster notes. "All of these can be caused by different conditions that require different kinds of treatments and may or may not respond to the same medications."
As big as the problem is now, experts expect the number of Americans with Alzheimer's disease to grow to as many as 7 million in coming decades, as the population ages. So the need for a good diagnostic test -- and better treatments -- will only get more pressing.
Researchers have already tried using other medical imaging techniques to detect the disease, with disappointing results. Up to now, magnetic resonance imaging (MRI) and computed tomography (CT) scans only rule out other disorders – they can't positively detect Alzheimer's.
"One of the challenges of trying to diagnose Alzheimer's disease is that it doesn't cause big changes that are visible on MRI and CT scans," says Foster. "So PET imaging has a great advantage because it shows a specific pattern that differs whether a person is experiencing normal aging, Alzheimer's disease or other kinds of dementias. It helps us determine which of these diseases is present, and gives doctors a good idea about how they should be treated."
PET studies at the U-M; the University of California, Davis; the University of Pennsylvania; and the University of Washington have been performed with funding from the National Alzheimer Coordinating Center, part of the National Institute on Aging.
In one study, Foster and his colleagues showed how they were able to tell Alzheimer's disease from a disorder called frontotemporal dementia, using PET scans from 45 patients, software to analyze the scans, and autopsy results from the same patients that gave a definitive diagnosis.
They also showed that using the software package, they could compare PET scans from different patients at different medical centers, and even compare scans taken on different PET scanners of various levels of sophistication. This will allow more studies to be done at PET scanning centers around the country to gather more evidence about how useful PET could be.
"PET imaging has great potential to aid diagnosis of patients with memory problems," Foster explains. "We've been able to identify changes that occur before patients themselves may recognize those problems. And we understand from PET scans what parts of the brain are most damaged in different disorders, and how these changes relate to patients' symptoms."
About PET scans
To the untrained eye, PET scans look irregular spots of rainbow colors on a black background. But for physicians, the scans hold crucial information about the level of chemical activity going on in different regions of the brain -- areas that control or contribute to all the functions of life.
The scans are made by injecting the patient with a form of sugar that has been altered to carry a weak, short-lived radioactive element. The sugar hits the bloodstream and flows to the brain, which needs huge amounts of energy to keep all its nerve cells running.
The most active areas of the brain need the most sugar -- while damaged and less active areas need much less. By detecting the weak radiation signal from the sugar molecules as they travel throughout the brain, PET scanners can make a picture of brain cell activity. The resulting scans show the level of activity using a scale of colors; red and orange for high activity, and blue and purple for low.
Doctors can compare a patient's own PET scan, showing areas of high and low activity, with maps of the structure and function of the different areas of the human brain, and knowledge about which brain regions Alzheimer's usually strikes earliest and hardest. Taken together, this analysis can tell them the extent of the damage, and the specific disease a patient has.
For example, areas of the brain involved in thinking and understanding the world around oneself are often damaged in Alzheimer's disease, resulting in memory loss and confusion. But areas involved in movement and the senses are not usually affected, so if a PET scan shows damage in those areas, a different disorder may be to blame.
Foster hopes that as evidence from research builds, PET scanning will become a part of the standard procedure for diagnosing patients with suspected Alzheimer's disease, and that insurance companies will begin to pay for their members to have PET scans for this purpose. He also foresees that the number of hospitals with PET scanners will continue to grow, as the usefulness of the scanners in diagnosing many diseases is proven.
In the long run, Foster also hopes that scientists will use the information from PET scans of Alzheimer's brain chemistry to develop new medications. "Once we can identify what kinds of chemicals are lost or changed in the brains of people with Alzheimer's disease, then we can design drugs to return the brain chemistry to normal," he explains.
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