Bret S. Stetka, MD; Gary W. Small, MD


July 03, 2014

In This Article

Editors Note: Following the American Academy of Neurology (AAN) 66th Annual Meeting, held in Philadelphia, Pennsylvania, from April 26 through May 3, 2014, Medscape interviewed dementia expert Gary W. Small, MD, on Alzheimer disease advances presented at the conference, along with other promising work in the field.

Amyloid Imaging: Any Point?

Medscape: A study that seemed to receive a lot of press at the AAN meeting this year was the florbetaben imaging study,[1] showing that amyloid imaging aligned with pathologic findings. Can you speak to the potential importance of this work?

Dr. Small: It's helpful to know the pattern of amyloid accumulation in the brain as it ages. Amyloid deposits are a key pathologic feature of Alzheimer disease. This kind of information offers us opportunities to make earlier diagnoses and treat people before there is tremendous progression of neurodegeneration.

Some of the challenges that we face are that the amyloid scans are often positive in people without symptoms -- up to 30% of the time in some studies. The question for the individual is: How is it helpful if I'm in my mid-40s and I have a positive amyloid scan? Until we link such neuroimaging tools or other diagnostic findings with treatment outcomes, they probably won't be used as extensively as some people might expect.

In other words, we would like to find a test that would dictate treatment, much like a cholesterol level informs a physician that prescribing a statin drug will lower a patient's future risk for a heart attack or stroke. Whether it's an amyloid scan or some other kind of test, we would like that tool to inform the patient and the physician that a certain treatment course will make a difference to the patient's future brain health.

Medscape: Right now, are clinicians outside of academia ordering these PET scans? Does it provide any treatment benefit at this point if you catch amyloid deposits, say, 10 years earlier?

Dr. Small: I don't know who is ordering these scans in clinical settings. Some doctors may be doing that, but because insurance does not cover it, I would imagine that not many scans are being done. They are difficult to interpret for the individual patient.

If a person is just experiencing normal aging and mild memory complaints, and the physician decides to get an amyloid scan, the patient can end up feeling anxious about the findings. Now the patient is worried about what is going on in his brain if his symptoms change. A study looking at APO e4 (the genetic risk for Alzheimer disease) found that when people were informed that they were APO e4 positive, they actually performed worse on cognitive tests than people who were APO e4 positive without being informed of it.[2]

Medscape: Presumably this was due to stress or the reaction to hearing the news?

Dr. Small: You would think that is probably the case, although it's unclear, because other studies have found that people who hear their APO e4 test results aren't any more anxious or depressed regardless of whether the results are positive or negative.

There is a lot we still don't know about the psychological effects of being informed of your test results. I have seen in some situations that when people find out they are APO e4 positive, it motivates them to live a healthier lifestyle to protect their brains. There can be lots of different outcomes.

Medscape: Say someone has a family history, and gets a positive amyloid scan at age 40 or 50 years. Would you start them on pharmacotherapy? Has any efficacy been demonstrated for early treatment?

Dr. Small: That is definitely premature with an amyloid scan. There are much more data on fluorodeoxyglucose (FDG) PET scans. If someone had one of those scans and it showed mild cognitive impairment, there is a very high likelihood that the person will develop dementia within a few years. Even without the scan, many doctors will put patients with mild cognitive impairment on cholinesterase inhibitor drugs, using them off-label. In some cases, there is a good outcome; in other cases, it's not as clear.

The systematic studies have not yielded clear results. One of the largest studies[3] found that donepezil lowered the rate of conversion of mild cognitive impairment to dementia after 1 year compared with placebo, but after 3 years, there was no difference between the drug group and the placebo group.


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