Miller promoted unsubstantiated claims about "Weapons of Mass Destruction" on the front page of The New York Times, providing legitimacy for going to war against Iraq. Kolata’s recent series of articles promoted the controversial push to screen healthy, asymptomatic seniors for amyloid plaques in the brain.
However, the assumption that those plaques are the causal evidence for diagnosing Alzheimer’s Disease is a matter of intense controversy.
Kolata’s glowing profile of Dr. Daniel Skovronsky, whose company, Avid Radiopharmaceuticals, has much to gain from widespread screening, is but a promotional piece that could have been written by a PR agency.
See: Promise Seen for Detection of Alzheimer’s , June 23, 2010
Kolata’s articles, Drug Trials Test Bold Plan to Slow Alzheimer’s , July 16, 2010 and Rules Seek to Expand Diagnosis of Alzheimer’s, July 14, 2010, are a ringing endorsement for the new diagnostic guidelines proposed by the National Institute on Aging in collaboration with the Alzheimer’s Association.
The proposed guidelines rely on screening for amyloid beta–even as there is growing skepticism among experts in the field about the validity of the amyloid theory as the cause or definitive biomarker for Alzheimer’s.
The recommended tests are: PET scans, which merely detect amyloid plaques; and spinal taps, which measure tau and amyloid. Yet, post mortem analyses have shown that some people with dementia have plaques, others, do not. And some people without dementia have plaques. So, the tests pose high risk of overdiagnosis.
Furthermore, the invasive tests pose risks–even at prestigious academic centers: PET scans pose potential risk from radiation, and exposure to impure (i.e., contaminated) radio tracers–as has been documented by the FDA’s investigation of Columbia University’s PET imaging lab. Spinal taps are painful and to prevent harm, they require expertise which is not routinely available.
REALITY CHECK: Dr. Sanjay Pimplikar a neurologist at the Cleveland Clinic argues against the use of these tests to diagnose Alzheimer’s in a New York Times OpEd piece (below) because their predictive potential is uncertain, at best.
"we now know that roughly one-third of all elderly adults have such plaques in their brains yet function normally. And eleven clinical trials, recently made public by a group of drug companies, that were aimed at reducing these plaques in Alzheimer’s patients all failed to show cognitive improvement, even when the brains were cleared of plaques."
As Peter Whitehouse , MD, PhD a neurologist at Case Western, and the co-author of The Myth of Alzheimer’s, notes on his blog: "we still do not know what amyloid-related proteins do normally in the brain. Past trials have shown safety issues and have not demonstrated efficacy."
Indeed, even drug-makers have acknowledged publicly that their years of effort to develop an effective drug to treat Alzheimer’s have been a failure:
"We really believe the drugs are failing because we honestly don’t understand the disease."
See: Wall Street Journal, Shirley Wang, Drug Makers Will Share Data From Failed Alzheimer’s Trials, June 11, 2010.
posted here.
Although a rational, empirical- approach would dictate that years of fruitless effort of seeking effective treatments by focusing on amyloids as the single cause of Alzheimer’s is no longer sustainable, "the reasoning behind [the proposed NIA/ Alzheimer’s Association diagnostic guidelines] is still mired in the “single protein (plaque), single drug, single cure” mentality."
Much like the diagnostic / treatment guidelines in psychiatry–i.e, the DSM-V–which are commercially-driven, crafted by psychiatrists with considerable financial conflicts of interest–the new Alzheimer’s diagnostic guidelines are commercially driven, without regard for patient’s best interest.
REALITY CHECK: Dr. Whitehouse notes that Alzheimer’s "is proving to be quite heterogeneous and resistant to a singular pathogenic target…Anti-amyloid drugs have engineered the removal of amyloid from the brain, but none have led to improvements in cognition and functioning (and have, in some cases, caused lethal encephalitis)."
He suggests that: "Odds are that plaques are a downstream manifestation of lifelong damage rather than being causal. Thus, a scan that shows us plaques on the brain doesn’t really do much except make a lot of money for whoever is doing the testing."
Kolata’s reports entirely ignore the skepticism among experienced experts in the field–including the particularly sobering acknowledgment by drug manufacturers: all the drugs targeting beta amyloid and plaques have failed to improve patients’ deteriorating cognitive function.
Instead, Kolata quotes as Gospel, Dr. Paul Aisen, who claims that 90% of scientists believe Alzheimer’s is “caused” by an amyloid problem. He eagerly "foresees a day when people in their 50s routinely have biomarker tests for Alzheimer’s and, if the tests indicate the disease is brewing, take drugs to halt it." Kolata’s report makes no mention about Dr. Aisen’s copious financial conflicts of interest.[2]
REALITY CHECK: Since there is no cure, not even effective treatments for Alzheimer’s, and no proven preventive measures against the onset of the disease or its progression–what possible benefit does screening to detect amyloid plaques have for seniors?
Indeed, as Dr. Richard Mayeux , a Columbia University neurologist points out:
“It’s not going to be helpful in diagnosis because a lot of people without Alzheimer’s have plaque that can be seen on scans. These people may go on to develop Alzheimer’s someday, but more study would have to establish that for it to become a definitive diagnostic test, rather than a tool to monitor plaque levels in research.”
REALITY CHECK: The new criteria for early diagnosis, based on early screening will hugely inflate the number of people diagnosed with Alzheimer’s–predictions estimate a two- to threefold increase. The proposed screening is EXPECTED to lead to many false-positive diagnoses. Indeed, the authors of the NIA/ Alzheimer’s Association proposed guidelines acknowledge that the earlier a diagnosis is made the less certain it is. As a result, people without the disease will be mislabeled and "treated" with drugs of little or no value.
Dr. P. Murali Doraiswamy, a psychiatry professor and Alzheimer’s disease researcher at Duke University seems of two minds: he applauds the proposed diagnostic screening but acknowledges that they will have "implications for everybody alive, anybody who is getting older.” Among other things, he said, "it will encourage a lot more testing… diagnosis rates, like testing rates, only go in one direction — up.”
He went on to say, “We ought to be cautious that we don’t stimulate all this testing before we can give people something to manage their disease. There is no point in giving them just a label.”
No one acknowledges the very real risk for people "diagnosed" with Alzheimer’s: the diagnosis–whether substantiated or not–is a cause for irrevocable denial of insurance. The earlier the diagnosis the greater the harm resulting from screening.
The beneficiaries of the proposed expansive diagnostic Alzheimer’s guidelines will be drug companies and the Alzheimer’s industry who will make fortunes by pathologizing millions of healthy young elderly people. Drug companies that failed to develop drugs that improved the condition of patients with the disease, wiill instead market drugs to unaffected people who would be screened and labeled as "probably" on their way to developing Alzheimer’s.
But what about the resources wasted on expensive screening and clinically ineffective interventions that could otherwise be used for honest scientific research to identify the underlying complex causes that trigger a disease that manifests as impaired memory, confusion, cognitive impairment and cascading brain damage–what we call Alzheimer’s?
And what about the psychological devastation for people misdiagnosed? Will the promoters of mass screening bear responsibility for the emotional pain and suffering incurred by a misdiagnosis of a debilitating disease?
Below, Dr. Pimplicar’s OpEd, followed by a synopsis of the 2010 award winning article by Dr. Rudy Castellani in the Journal of Alzheimer’s Disease which rebukes the proponents of the amyloid causal theory for Alzheimer’s; followed by an unpublished letter to the NYT editor by Dr. Peter Whitehouse; and a commentary by Geoff posted on the NYT blog about the experts Gina Kolata quotes without ever mentioning their financial conflicts of interest.
References:
1. "If Kolata’s reporting faults were only a reflection of her own journalistic shortcomings, that would be bad enough. But to the extent that they reflect the attitudes of the Times as an institution, they suggest a Times policy toward coverage of controversial products of technology, pro-corporate and fundamentalist in its approach to scientific inquiry."
See: Gina Kolata: What’s Wrong With the New York Times’s Science Reporting? a critique by Mark Dowie, The NATION July 6, 1998 that still resonates.
See also, SourceWatch, which includes a bibliography of her controversial articles and a bibliography of articles criticizing her biased reporting–including a letter from her own doctor, dated Jan. 2010.
2 The NIH Consensus Development conference, April, 2010, lists the following financial relationships for
Dr. Paul Aisen:
Medivation, Neurophage: Stock options, consulting fees received during role as consultant/advisor;
Pfizer Pharmaceuticals, Baxter: Research grants received during role as PI; received sonsulting fees during role as consultant for Elan Pharmaceuticals, Roche, Novartis, Eli Lilly & Company, Martek, Amgen, Genentech, Abbott Laboratories, Bristol-Myers Squibb, Schering-Plough, Wyeth Pharmaceuticals, Eisai, Glaxo SmithKline, AstraZeneca, Bellus, Merck Pharmaceuticals, Astellas Pharma, Dainippon Pharmaceutical, BioMarin, Solvay, Otsuka, Daiichi Sankyo
Vera Hassner Sharav
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The New York Times
OpEd
July 19, 2010
Alzheimer’s Isn’t Up to the Tests
By SANJAY W. PIMPLIKARCLEVELAND
A PANEL of medical experts from the National Institute on Aging and the Alzheimer’s Association last week proposed changes in the way doctors diagnose Alzheimer’s disease — including the use of so-called biomarkers, tests like PET brain scans and analyses of spinal fluids to promote early detection of the disease. Although these recommendations are well intentioned, evidence suggests that it would be a mistake to adopt them at this time. To understand why, it’s important to recognize what these tests mean, in what context the information will be used and what experience has shown us.
First, about the diagnostic tests: A PET scan detects clumps of a deformed protein called amyloid beta, commonly known as plaques. The presence of these plaques has been a gold standard of Alzheimer’s pathology since 1906, when Dr. Alois Alzheimer first identified them in a patient.
However, we now know that roughly one-third of all elderly adults have such plaques in their brains yet function normally. And eleven clinical trials, recently made public by a group of drug companies, that were aimed at reducing these plaques in Alzheimer’s patients all failed to show cognitive improvement, even when the brains were cleared of plaques.
Thus, the presence of plaques cannot predict with any accuracy or specificity that an individual is going to acquire the disease — and researchers are increasingly looking beyond the amyloid hypothesis for an adequate explanation for Alzheimer’s.
Another test being recommended by the panel is spinal fluid analysis — which measures the relative levels of two proteins, tau and amyloid beta. This method does seem quite promising, but its predictive potential remains uncertain.
There are also practical issues to be considered, not least of all the high cost of these procedures. What’s more, the spinal tap procedure is not easy to perform and is painful to undergo, and it is a long way from becoming a routine diagnostic tool. Dr. Janis Petzel, a geriatric psychiatrist in Maine, has noted how unfeasible this test is in “nonacademic, rural or non-Western settings”: “I pray that cerebrospinal fluid findings will never be part of diagnostic criteria for Alzheimer’s disease,” she wrote.
The diagnostic tests themselves can carry a risk of side effects. General imaging scans can expose patients to radiation, for instance; an invasive spinal tap could result in infection or damage to tissue. But there is also the psychological risk of false positives and misdiagnoses that greatly distress patients, at least until further tests show they do not have the disease.
This danger of overdiagnosis is very real, as the history of treatment for prostate cancer shows. A study last year about the prostate-specific antigen test found that in the two decades after the test was introduced, prostate cancer was detected in more than 1 million additional men, many of whom were likely overtreated.
Last, the most dreadful thing about Alzheimer’s disease, next to the slow deterioration of cognition, is that we do not yet have a cure and none seems to be on the horizon. So, even if the new recommendations rendered the diagnosis earlier and unassailable, there is no therapeutic avenue to use this information to effectively treat the patient. Many individuals would simply prefer to be spared the emotional trauma of a diagnosis if no treatment exists.
Taken together, these reasons suggest that the panel’s recommendations are likely to increase the emotional burden on individuals and the financial burden on society without providing proportional benefits. The doctor’s most basic tenet is that of primum non nocere — first, do no harm. Until we have a more definite idea about what causes Alzheimer’s, early-detection tests may do patients more harm than good.
Sanjay W. Pimplikar is an associate professor in the department of neurosciences at the Cleveland Clinic’s Lerner Research Institute.
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Best paper of 2010 in the Journal of Alzheimer’s Disease:
Dr. Rudy Castellani’s paper, “Reexamining Alzheimer’s Disease: Evidence for a Protective Role for Amyloid-β Protein Precursor and Amyloid-β,” (J Alzheimers Dis 18, 447-452, 2009) is a synthesis of pathogenic hypotheses and their relationship with presumed causative lesions (e.g., amyloid-β) and molecules (amyloid-β, amyloid-β protein precursor).
His assessment of the state of knowledge is a somewhat cynical and stinging rebuke (necessarily so in his view) of the major school of thought in Alzheimer’s disease pathogenesis, which he describes as reductionist and fundamentally backward.He bases this interpretation on the pathology, and the relationship between pathology and disease that clearly indicates plaques, amyloid-β protein precursor processing, and amyloid-β metabolism, as effect, or “host response,” rather than cause.
He goes on to provide evidence for the beneficial and protective effects of amyloid formation across species, and its role as antioxidant, metal chelator, and oligomer detoxifier.Perhaps the most important contribution of this article overall is the previously unemphasized point that the pathology of chronic diseases in general, and Alzheimer’s disease in particular, tends to distract from upstream processes, and instead encourages the characterization and continued pursuit of small molecule cascades that are, at best, epiphenomenal.
~~~~~~~~~Letter to the Editor:
The proposed diagnostic guidelines for Alzheimer’s (NYT July 14 2010) deserve greater scientific, clinical, economic, and ethical scrutiny. Do they represent real hope, or more hype? Who do they benefit, not clearly patients?
The authors themselves say (fn3) “These quantitative techniques are, and will continue to be in evolution for some time… The priority of one biomarker over another … has not been established … Therefore practical use … must follow local best-practice guidelines…”
Are these guidelines ready for general clinical use?
There is little point in using multiple forms of invasive and expensive research tests to assign a frightening and imprecise set of diagnostic labels to millions more people, especially without effective therapies being available.
The many unfulfilled promises to develop drugs should serve as a warning that this field’s marketing is more advanced that its science.Even the esteemed, recently deceased, pioneering NY gerontologist and Alzheimer’s promoter, Robert Butler, came to realize late in his life that what we now call Alzheimer’s is more than one disease about to be cured.
Peter Whitehouse, MD
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Comment
This series of Alzheimer’s articles is basically marketing dressed up as research, and breathless reportage by Gina Kolata about one hypothesis of how Alzhimer’s works, a hypothesis which is not shared by all. Kolata gives much attention to this hypothesis and quotes only proponents of the amyloid hypothesis, including 3 physicians with ties to Elan Pharmaceuticals. Gandy, Aisen, and Selkoe all have a relationship with this pharmaceutical company that is developing an Alzheimer’s drug and Selkoe is certainly one of the big names in this type of research. He has a number of critics, who may or may not be correct about whether his research is impartial, but certainly some explanation of this larger dynamic is warranted in a NYT piece. There is evidence that the attention given to the amyloid hypothesis crowds out funding for research on other hypotheses of Alzheimer’s development, and that the big names that promote the amyloid hypothesis (including Selkoe) are part of the reason that so much funding goes to this type of research. Kolata’s piece can only help those proponents of the amyloid hypothesis, and sweep under the rug legitimate questions about competing interests. The question is whether physicians with such obvious financial stakes in these expanded criteria for drug use and testing should be given the credence that this article gives them. At least the information should be given to the reader, so that the reader can decide how to think about these complex issues.
(http://www.tangledneuron.info… http://www.bmj.com… http://www.bostonphoenix.com/archives/1999/documents/00521742.htm).Posted by Geoff, Boston
July 17th, 2010
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