Health News Review

The following is a guest post by Linda Furlini, PhD, who works in the research ethics office of McGill University Health Centre in Montreal.

Since the late 1980′s, I have developed a voracious appetite to learn all there is to learn about Alzheimer’s disease because both of my parents at the age of 60 were affected by it, even though neither had a family history of the disease. In the process, I have gathered what has amounted to mountains of disinformation on Alzheimer’s disease. As I perused the many articles I had collected, it became glaringly apparent that, in that quarter century, little has changed: consistent unfounded claims have been made about the latest “breakthroughs,” “discoveries,” and “understandings.” Each claim creating false hope, or worse, harm and confusion. When I reflect on all those bogus claims, I become overwhelmed with frustration, anger and dismay.

So, when I listened to a recent CBS evening news report (June 19, 2012), these feelings returned with a vengeance.

Dr. LaPook presented a new test that could diagnose and predict the occurrence of the Alzheimer’s disease with absolute certainty. During the segment, we meet a man named Alex who undergoes the test. He is described as a scientist and a highly intelligent man, particularly worried about his self-reported cognitive decline in light of the fact that his mother had Alzheimer’s disease. Undoubtedly, this type of worry would resonate with anyone familiar with the ravages of this disease. We are told that this new test, “Would tell him for sure” if he had Alzheimer’s disease. We are then informed that the test result shows “He does not have Alzheimer’s disease.” Recently, the FDA approved florbetapir, a radioactive dye that detects amyloid plaques, a protein in the brain that some scientists theorize play a role in the development of the disease. Through the use of a PET scan, this dye showed Alex’s brain showed no presence of amyloid plaques. We see a visibly relieved Alex.

But what did this test really tell Alex? The test showed that no amyloid plaques were detected, but nothing more. What the test failed to do was to tell Alex that: 1) although he appeared not have Alzheimer’s disease, it was not absolutely certain he was free of the disease; 2) some people who have these amyloid plaques do not demonstrate symptoms of the disease; and 3) it was unknown whether he would develop this disease in the future.

We lack evidence to determine whether the plaques develop before the onset of symptoms or once the disease is already established. Still, we do know enough about the disease to appreciate that although the plaques may be apparent, a person may not demonstrate any symptoms of the disease. We also know enough to realize that the lack of amyloid plaques is not predictive and that the disease may manifest itself in the future. So why not present this information in the CBS report?

Justifiably, patients, families and society are desperate to prevent Alzheimer’s disease, a scourge that many of us will face in this century. In the rush to develop preventative disease drug trials, the NIH added a new phase to their diagnostic guidelines, named “Preclinical Alzheimer’s.” Unreliable and unproven tests to diagnose the disease, such as the one Alex took, will be used to recruit people into these trials. An important question that begs to be asked: how can we trust the drugs that will be developed as a result? What are the ethical implications for those that are determined to have “Preclinical Alzheimer’s” and never develop the disease and, conversely, those whose tests show no evidence, but do have symptoms? For excellent reading on this topic, see Covinsky and Kutschenko.

Alzheimer’s disease is complex, but it is in the pharmaceutical industry’s interest to oversimplify it. Clearly, the test reported on by CBS demonstrates medical progress. But, it should have seriously questioned the value of the test. Instead, unsuspecting, desperate and worried people will be lured into believing more than they should about it and recruited into clinical trials built on uncertainties and ambiguities. Shame on CBS for adding yet more material to my mountains of disinformation, and for failing to address the need for better scientific research.

Covinsky, K. (2011). Caution on Diagnosing Preclinical Alzheimer’s Disease. The Hasting Centre Report,

Kutschenko, L. (2012). Disgnostic misconceptions? A closer look at clinical research on Alzheimer’s disease. Journal of Medical Ethics, 38, 57-59


Dr. Jon LaPook posted on June 25, 2012 at 5:07 pm

I greatly appreciate the thoughtful posting by Dr. Furlini. I have done many segments on Alzheimer’s Disease over the past years and have always been keenly aware of the importance of avoiding hype and false hope. We would loved to have had more time to go into the nuances of the many ethical issues raised by testing for Alzheimer’s, including the problem of people doing home kits – without adequate genetic counseling – to test for the APOE4 allele. Unfortunately, as is often the case with network news, we did not have as much time as we wanted and we had to make tough decisions about what to include.

Dr. Furlini’s first sentence is not accurate: “Dr. LaPook presented a new test that could diagnose and predict the occurrence of the Alzheimer’s disease with absolute certainty.” We very carefully presented the test as one that could tell our patient that he did NOT have Alzheimer’s but did not say the test can diagnose Alzheimer’s disease with absolute certainly. In fact, Dr. Furlini correctly points out that the presence of amyloid does not mean a person has Alzheimer’s. About 20-30 percent of Americans over the age of 65 have amyloid on scan but do NOT have obvious evidence of dementia; people in this group are being studied to try to determine what happens to them over time. We thought that just mentioning this statistic without having adequate time to explain it would be confusing in a piece that – unfortunately – was time-limited.

The main point of our segment was that the negative amyloid PET scan test meant Mr. Dreyfoos does not have Alzheimer’s disease right now and that knowledge has dramatically changed his approach to the next chapter of his life. Dr. Sam Gandy, Mr. Dreyfoos’ neurologist at Mount Sinai and Director of Mount Sinai Center for Cognitive Health, just confirmed this when I emailed him a link to Dr. Furlini’s post. Dr. Gandy’s team developed the first amyloid lowering strategy in 1986 and he has been continuously funded by the NIH since then to study the role of amyloid in Alzheimer’s. He just emailed me:

“Her statement ‘We lack evidence to determine whether the plaques develop before the onset of symptoms or once the disease is already established’ does not agree with current research or current conventional wisdom. I think that the salient point is that current conventional wisdom indicates that positive amyloid scans PRECEDE cognitive decline by up to 15 yrs, maybe even longer. Patients with cognitive decline and negative scans usually have some other explanation for their cognitive decline. Could there be exceptions? There are some rare situations in which a negative scan is due to some technical issues about which forms of amyloid (fibrils vs oligomers) predominate, but these are VERY rare (i.e., so far as I can find, there have been exactly 2 case reports in the past 10 years of working up amyloid imaging ligands in thousands of subjects worldwide).”

Jon LaPook, MD
Medical Correspondent, CBS Evening News with Scott Pelley
Clinical Professor of Medicine
Columbia University Medical Center

Linda Furlini posted on June 26, 2012 at 6:50 am

As the author, I want to thank Dr. LaPook for his thoughtful comments and wish to respond.
1. I regret that my first sentence expressed what I believed to be the impression viewers would get. I should have noted that it was an observation. However, the headline stated my main point more emphatically and that is where Dr. LaPook and I disagree: he stated that the test proved with certainty that Mr. Dreyfoos, the patient, did not have Alzheimer’s because his brain scan showed no detectable amyloid plaques. Unfortunately, evidence indicates that it is unclear whether amyloid plaques maybe a precursor to, or a result of, Alzheimer’s disease (see, for instance,
2. The report lacked information that enlightened viewers about the limitations of the test to diagnose the disease or predict its occurrence in the near or distant future. Dr. LaPook also noted that he had no time to mention that amyloid plaques are detected in some people who remain asymptomatic. This is unfortunate, for a report that contains incomplete information can be as harmful as one that contains inaccurate information.
3. I appreciate that Dr. LaPook took the time to contact Dr. Gandy about my comments. However, his points do not advance this discussion. Although Dr. Gandy has worked very long and hard investigating the relationship between Alzheimer’s disease and amyloid plaques, his “research” and “current conventional wisdom” do not constitute certain evidence. Many researchers have challenged the amyloid lowering strategy and the amyloid hypothesis altogether ( and, strongly suggests that this is a reason that current drug trials have failed dismally.

Jim Kling posted on June 26, 2012 at 11:21 am

I was unimpressed with this analysis. I am a medical writer with over ten years of experience, and in my view, this report was just fine. There certainly was no hype that I could see.

“Although he appeared not have Alzheimer’s disease, it was not absolutely certain he was free of
the disease

So, they could have said the test can give a false negative. Okay, that’s fair. Is it a high rate? Doesn’t sound like it based on the use of the phrase ‘absolutely certain.’ Not a big deal.

2) some people who have these amyloid plaques do not demonstrate symptoms of the disease

Irrelevant. Alex received a negative result, not a positive, so what does a false positive have to do with this report?

3) it was unknown whether he would develop this disease in the future.

So, every story about a cancer diagnostic should end with: but this doesn’t guarantee you won’t get cancer in the future?

I’m all for justified media criticism. But this was was a real reach.

Gary Schwitzer posted on June 26, 2012 at 11:50 am

We welcome the exchange of opinions. Here are some that appeared on Twitter:

UCSF geriatrics clinician-researcher Ken Covinsky (who goes by @geri_doc), wrote: “Nice post. Irresponsible CBS story.”

@epatientDave wrote: “Shame! CBS/@DrLaPook claims Alzheimer’s scan=medical certainty; bogus.”

Sam Gandy MD PhD posted on June 26, 2012 at 2:39 pm

On the topic of the accuracy of Amyvid in detecting amyloid: in the Clark et al study published in JAMA that formed the basis for the FDA approval of the scan, Amyvid correctly identified the presence or absence of amyloid in 96% of 29 subjects who underwent autopsy at mean of 99 days (range, 1-377 days) from scan to death. Fifteen of those 29 individuals (51.7%) met pathological criteria for Alzheimer disease. Future studies could show something different, but, based on what we know now, Amyvid can be said to be 96% accurate in identifying true positives (with amyloid at autopsy) and true negatives (no amyloid at autopsy).

Sam Gandy MD PhD posted on June 26, 2012 at 3:05 pm

Dr Furlini and I agree but only up to a point. We have come as far as we can with current genetic strategies and with modeling Alzheimer’s in mice, and, at this point, there are only a few ways for us to understand the cause(s) of common sporadic Alzheimer’s and the role of amyloid therein:

(1) The New York Genome Center is sequencing the complete genomes of 50 patients with sporadic Alzheimer’s disease in search of de novo mutations such as the ones recently found in autism. Hopefully this will provide breakthrough revelations.

(2) Creation of mature human Alzheimer’s neurons by redifferentiating iPS cells or fibroblasts. These neurons might suggest to us properties that underlie common sporadic Alzheimer’s disease. For example, one such study claims to have found abnormally dilated bubbles called endosomes in such human Alzheimer’s neurons. This is potentially a new clue to common sporadic Alzheimer’s.

(3) 1-3% of Alzheimer’s disease is early onset and completely genetic. The genes that cause this rare form of Alzheimer’s are either the amyloid gene itself or the gene for an enzyme that makes the deposited amyloid fragment from its parent protein. These forms of Alzheimer’s have the best chance of being caused by amyloid. In these families, the age at onset is predictable and the mutations are identified. Therefore, there are now living around the world several thousand young and middle aged
people who know that they will develop Alzheimer’s disease and they know roughly when that will begin.

Some of these young and middled aged people with amyloid-causing mutant forms of Alzheimer’s disease have enrolled in trials in which they will begin receiving an antibody that is known to clear amyloid from the brain. If the amyloid hypotheses is correct, then preventing amyloid buildup in the brains of these presymptomatic subjects with amyloid-causing mutant forms of Alzheimer’s disease will prevent them from ever getting Alzheimer’s. This trial/ experiment will cost a few hundred million dollars and will take at least 5 yrs, maybe 10 yrs, maybe more. If the antibody prevents amyloid buildup but the subjects dement anyway, that will establish that there are other factors aside from amyloid buildup that kill neurons in Alzheimer’s.

The amyloid naysayers, such as Dr Furlini, argue that this is a waste of time and money. Some say that early onset familial Alzheimer’s is so rare that we should not even study it. I would argue that this position is cynical and irresponsible. At this point, we know more about treating amyloid than we do about treating any other feature of Alzheimer’s. Given that a definitive answer about the role of Alzheimer’s is achievable and within reach, I can see no justification for abandoning this path until we have resolved the issue, one way or the other.

I would never argue that amyloid should be pursued exclusively. I can imagine plausible pathways in which neurons are killed by calcium or oxidation, and amyloid is generated as a side product, but the genetics so far dont point in that direction. I am happy to see tangle research, stem cell research, all receive investment and flourish. I am even happy to have it proven that amyloid is not the key to Alzheimer’s. But I am only happy to abandon amyloid when there are hard data showing that
Alzheimer’s develops even when amyloidosis is prevented and that the amyloidosis is completely non-contributory. I am not happy to give up on the basis of nihilism.

Scientists are often assumed to be sequestered away from patients and lacking in sensitivity to the very real suffering that goes on. I have seen Alzheimer’s not only as a scientist but as a family member and caregiver and as a physician. For 15 yrs, I visited a demented grandmother in a nursing home every Sunday. For most of that time, she did not recognize me or anyone in the family. Up and down those long halls were room after room of patients with dementia, having been reduced to persistent vegetative state, eyes occasionally open but with no capacity to perceive or engage their environments.

Every week even now, I spend much of my time giving bad news to families who bring loved ones in, hoping against hope that their loved one’s changes in memory or personality are not indicative of Alzheimer’s. Amyvid now makes it possible for me to say with 96% certainty whether the diagnosis at that moment is indeed Alzheimer’s. That qualifies as a breakthrough in my book, not because a cure is revealed, but because. for the first time, we can see the enemy and measure the effects of our experimental drugs. Only now, with the enemy squarely in our sights, can we have real hope of vanquishing Alzheimer’s disease, once and for all.

Paul F Davis posted on July 5, 2012 at 4:40 pm

Thanks for sorting through the bogus claims.