Unraveling the Mystery

As Robert C. Borwell Professor of Neurological Sciences and director of the Rush Alzheimer's Disease Center, David A. Bennett, M.D. is a nationally recognized authority on Alzheimer's disease and other neurologic conditions. Dr. Bennett is principal investigator of several studies funded by the National Institute on Aging, including the Rush Alzheimer's Disease Core Center, the Religious Orders Study, and the Memory and Aging Project. The Post spoke with Dr. Bennett about diagnosis, causes, and prevention of Alzheimer's Disease.

Q: When and how often do doctors suggest autopsy for confirmation of Alzheimer's disease?

Twenty years ago, we did it all the time. Today, we are so good at clinical diagnosis that we only recommend autopsy when unsure of the diagnosis or as part of a research study. To confirm a diagnosis of Alzheimer's Disease, a silver stain of brain tissue is performed, which shows the plaques and tangles. If at a specialized center, this test is routine.

Q: Is a blood test available?

No. Specialized centers offer highly experienced clinicians. If a specialist clinically diagnoses someone with Alzheimer's Disease, more than 90 percent of the time that individual has the disease. All other tests being done-brain scans, blood tests, genetic tests, PET and MRI scans-are either to search for another cause of dementia such as a stroke, brain tumor, or fronto-temporal dementia, or are research tools.

Q: How can people locate specialized centers?

The National Institute on Aging at the NIH hosts a website (http:/ /www.nia.nih.gov/Alzheimers/ Researchlnformation/ResearchCenters) listing specialized Alzheimer's Disease Centers. Another website is called the Alzheimer's Disease Education and Referral Center (ADEAR) at the NIH (www.nla.nih.gov/alzheimers), which offers information on where people can volunteer for research trials, publications, newsletters, and other information.

People who don't live near an Alzheimer's Disease Center can contact the Alzheimer's Association (www.alz.org) with chapters across the country that can steer you to the most reputable person in your area.

Q: Is brain donation important in helping Alzheimer's Disease researchers?

Running two of the largest studies in the world with organ donation, I can tell you organ donation is very important. The field has moved toward larger epidemiologic studies. In my studies, we have more than 2,300 older people without dementia, who agree to be tested every year. To enter the study, you agree to become an organ donor. Over time, study participants remain normal, develop mild cognitive problems, or full-blown Alzheimer's Disease. Through these types of studies, we can better understand what causes subtle memory problems in people without dementia-what occurs during normal aging.

We can also see how different structures in the brain interact. While Alzheimer's Disease changes are common, strokes and Lewy bodies which are usually seen in Parkinson's disease both contribute to memory loss.

We want to figure out how a risk factor causes Alzheimer's Disease. For example, if you have a genetic factor associated with the risk of Alzheimer's Disease such as ApoE4, we study what ApoE4 is actually doing in your brain to cause the development of the plaques and tangles. If we can understand those mechanisms, we might be able to intervene and prevent the development of the pathology of Alzheimer's Disease and the cognitive loss due to the pathology. In the end, Alzheimer's Disease is a disease you want to prevent, not treat after you get it. In short, organ donation as part of a comprehensive study is a crucial piece of the Alzheimer's research puzzle.

One of the changes, again, over the last couple of decades is that researchers are no longer looking for brain tissue from people they haven't studied during life, so we want to encourage people to enroll in a research project, some of which might require organ donation. That's the key piece. We need brain tissue from people who have enrolled in a study and underwent uniform evaluations like other people in the study. That's what makes the brain tissue most useful.

Q: Is there a certain age or other criteria when people should enroll in trials?

There are all kinds of criteria and all kinds of studies. For studies of organ donation, for example, where people enroll without dementia and are then followed, we enroll people over age 65. Clinical trials for Alzheimer's Disease tend to go down to about age 50, but other midllfe aging studies are going on. People interested in volunteering should contact their center and say, "I want to volunteer to help prevent Alzheimer's Disease."

Q: Is genetic testing at this point advisable?

In general, no. You can order a genetic test right off the Web. The test will tell you if you have a gene that predisposes you to Alzheimer's Disease. However, it is not a test for Alzheimer's Disease -- that test is basically cognitive testing -- but you can find out If you have a gene that predisposes you to AD. The real question is: what do you do with that information? Imagine being tested for the gene, finding out that you don't have it, and being relieved.

The problem is that most people who get Alzheimer's Disease do not have that gene, so it's a false relief. Of course, if you have the gene, your risk Is higher. It doesn't guarantee you'll get the disease; it means that your risk-which for all of us is already high-is just higher.

Q: Are researchers gaining ground in understanding the causes?

Absolutely. We've made tremendous strides in understanding Alzheimer's Disease. When the NIA Alzheimer's program started in the mid-1980s, all we basically knew was that there were plaques and tangles in the brain. Now we know what those plaques and tangles are made of and how they're formed. Symptomatic treatments have been approved by the Food and Drug Administration, and drugs are under investigation to slow the formation of tangles and plaques. We've identified many factors associated with risk of getting Alzheimer's Disease.

We're beginning to understand what risk factors that actually cause Alzheimer's disease are doing. With that information, we can think about prevention. We've made tremendous progress. We've identified a number of genetic mutations and one genetic risk factor. I don't want to say we're on the verge of solving it. A cadre of researchers across the United States, Europe, Canada, Australia, and Japan is working on Alzheimer's Disease. Solving Alzheimer's Disease is a partnership between the researcher, the funding agencies, and volunteers.

If you look at the demographic changes through the middle of the century, there will be more old people and more Alzheimer's Disease. The real push is for prevention. Prevention studies are expensive and take time.