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Q&A: State Of The Science On Early Alzheimer's Disease

Even as I write this, I can feel the biological hallmarks of Alzheimer's Disease building in my brain: the beta-amyloid plaques gumming it up, and the tau protein tangles snaking through the neurons. But a bit of paranoia is a small price to pay for the critical new understanding that scientists have gained about Alzheimer's Disease in recent years: that the brain pathology begins long before the forgetfulness shows up. Early brain pathology means early detection is possible, and early detection means the potential for blocking the disease before it turns into the terrible dementia that affects millions.

Dr. Reisa Sperling of Brigham & Women's
Dr. Reisa Sperling of Brigham & Women's

The biggest changes are that we’ve reconceptualized Alzheimer's Disease as a continuum. The first criteria published in 1984 only dealt with Alzheimer's Disease as a stage of dementia, which we now recognize to be at rather late stages of the disease process. The new criteria incorporate an earlier symptomatic stage called mild cognitive impairment due to Alzheimer's Disease. And the earliest stage, which we have called pre-clinical Alzheimer's Disease, is a new concept of the disease beginning in the brain prior to the clinical symptoms.

How would you sum up the state of the science on early detection of Alzheimer’s?

The pre-clinical stage is primarily detected through bio-markers. There have been tremendous advances over the past decade in being able to detect evidence of Alzheimer's Disease in the brain during life. These include PET scans for amyloid, cerebrospinal fluid tests, and both functional and structural MRI scans.

Is there any one particular holy grail in terms of research on early detection of Alzheimer's?

I don't actually think it will be one thing. I think that we know from the autopsy data that there are actually several processes in the brain involved, and I suspect that we will need a combination of biomarkers to detect these processes. But the holy grail would be finding the combination of biomarkers in people who are still cognitively normal that accurately predicts who will progress to Alzheimer's Disease dementia.

In terms of the existing ways for detecting Alzheimer's Disease early, I gather none of them are ready for prime-time in the clinic?

That’s correct. I believe we're getting closer to a number of tests but we need further work, especially on standardization, so that getting a PET scan or a spinal fluid test will give you the same value no matter where you have the test performed. But I think this will happen. In the same way you can measure someone’s blood pressure or blood glucose, we'll one day be able to say, 'This is the amount of amyloid and this is the nerve damage.'

How long away might those biological early detection tests be from the clinic?

For some biomarkers, we’re fairly close. For spinal fluid, there’s already an ongoing effort to standardize values across labs, which is progressing quite well, and I suspect we'll see something very similar for both PET and MRI scans.

If I feel a burning need to get tested nonetheless, are there clinical trials under way in the Boston area that would let me?

Absolutely. One study is the Harvard Aging Brain Study, in which we are following 300 normal older individuals — over 65 — with and without amyloid. There are a number of studies around the country, and a good place to find them is the Alzheimer's Association's "trial match," a website where an individual who’s normal or someone who’s affected clinically or their family can go online and match themselves to a study. In the Harvard study, we’re especially looking for people from diverse educational and economic backgrounds.

Do you have any particular warning for people who get tested in any way, whether in a trial or in a doctor’s office?

People should not expect to have bio-marker testing clinically at this point. For right now the diagnosis of mild cognitive impairment and Alzheimer's dementia will remain primarily a clinical diagnosis. There are some circumstances in which clinicians already use some of these biomarkers, but I don’t think they will become standard of care until further research validates their use in the community. That research is starting right now.

So your message to the general public on early detection using bio-markers is...?

This is coming, and it’s coming sooner rather than later. Some of these may be available within a year or two: There are a number of PET amyloid tracers in development; none have been approved by the FDA but there have been FDA hearings on them. And spinal fluid tests are available now but we don’t recommend their use routinely at this point. And MRIs are available widely and are already being used but thus far not in a very quantitative way.

At CommonHealth, we tend to focus a lot on health care costs, and I'm thinking millions of MRIs and spinal fluid tests and PET scans are going to add up to a lot of money.

I am very worried about health care costs and I think that there will come a point where we need to prove that early detection is also cost savings. But that really depends on having a disease-modifying treatment.
There have been models already that suggest that if we could delay the onset of dementia by five years, we would cut Medicare costs related to dementia in half. It would be a huge savings. But again, we need both the test to detect Alzheimer's Disease and success in treating it. But I do believe that eventually it’s actually a cost win.

Let's end on a hopeful note! So far, attempts to thwart Alzheimer's Disease using drugs have been very disappointing. Does the new light cast on pre-clinical Alzheimer's open the way for new treatments?

In fact, this is exactly why we set out a new set of research criteria: to allow academia and pharmaceutical companies to be able to plan for prevention trials using a standard definition. I hope that these research criteria will allow us to begin clinical trials in pre-clinical Alzheimer's Disease very soon. We do have drugs that seem to have biologic activity against amyloid, and we believe that trying these drugs much earlier would have a much better chance of modifying the clinical course of the disease. In fact, there are a number of these efforts already being planned.
The main reason we pushed on these criteria was to allow us to do trials that are really prevention trials instead of treating people at what is probably the late stages of the disease. I’m very excited about that.

This program aired on April 19, 2011. The audio for this program is not available.

Carey Goldberg Twitter Editor, CommonHealth
Carey Goldberg is the editor of WBUR's CommonHealth blog.


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