Updated 5 August 2010
Following a media call hosted by Alzheimer's Association, The New York Times ran a second story on the revised diagnostic guidelines.
This is Part 1 of a three-part series. See Part 2 and Part 3.
4 August 2010. Every newspaper editor knows it: dare tinker with the established look and feel of the paper, and some readers’ initial response will be irritated, even vituperative, no matter how carefully the modernization was done. Something similar—though on a deeper, more serious issue—happened to perhaps the biggest news story of the International Conference on Alzheimer’s Disease, hosted 10-15 July 2010 at the Hawai’i Convention Center in Honolulu. There, three expert groups convened by the National Institute on Aging and the Alzheimer’s Association presented to the assembled research and clinical community draft results of their ongoing, year-long effort to incorporate scientific advances of the past quarter-century into a revision of the current diagnostic criteria for Alzheimer disease (AD). Published in 1984, these criteria predate much of what’s now known about imaging and biomarker research, about genetics, related diseases, and, indeed, the molecular pathophysiology underlying early AD. They are widely used and have never been formally updated.
In Honolulu, a panel of leading scientists addressed nearly 1,000 of their colleagues in the main lecture hall, and then spoke with attending reporters. For its part, the Association had issued a press release and made the revised criteria—all 30 pages of them—freely available to reporters and the public. Even so, the story spun out of control. Some press reports implied, erroneously, that biomarker testing would triple the number of diagnoses starting this fall, driving up costs while needlessly upsetting people who would never get dementia and for whom nothing could be done anyhow. The issue prompted public concern among Alzheimer disease scientists who question the amyloid hypothesis, among medical practitioners, and among psychiatrists who questioned the wisdom of attempting a diagnosis when the person feels no “dis-ease,” i.e., is still at ease.
What happened? Most of all, what were the scientists really trying to say? And what do their colleagues think of the new criteria?
The scientific workgroups had broken the task of revising diagnostic criteria into three parts. One group, led by Guy McKhann of Johns Hopkins University in Baltimore, Maryland, took on Alzheimer’s dementia. A second group, led by Marilyn Albert, also of Hopkins, dealt with mild cognitive impairment due to AD, and a third, led by Reisa Sperling of Harvard Medical School, tackled preclinical AD. Stating that the underlying Alzheimer disease process advances continuously starting with a decade-long or maybe even longer asymptomatic period, the three sets of new guidelines each incorporate biomarker measurements. The guidelines gradually rely on biomarkers more and more the earlier in the disease process one goes. The workgroups posted them on the Web, and invite fellow clinicians to engage in a period of feedback throughout the month of August, before the guidelines are published in a peer-reviewed journal.
The key point of misunderstanding lay in the fact that the biomarker portions in the criteria for all three phases of AD are strictly for research purposes. At this point and for some years to come, the biomarker-driven criteria serve as a conceptual framework for testing and to facilitate therapeutic trials in secondary prevention. They are not meant for community physicians any time soon.
Can You Hear Me?
This was said explicitly. “I want to put a clear bright line between those criteria intended for general use by clinicians, and those criteria intended to be used as research criteria. These research criteria are not even available to us as we go over to the clinic to diagnose! This is hugely important with respect to how the world hears this issue,” Steven DeKosky of the University of Virginia told both scientists and the media. “We want to get out the message that we are trying to find ways to diagnose and treat earlier.” Alas, this was not universally heard. Some news stories mixed up what’s ready for prime time and what’s not, and lumped the recommendations for clinical use in with those for research use. And truth be told, the threesome of presentations at ICAD left this a bit vague. While the entirety of the preclinical criteria are meant for research only, and were unequivocally presented as such, there was less clarity at ICAD about the criteria for the MCI and dementia phases of the disease. For those two, the portion of each set of criteria dealing with biomarkers is also intended primarily for research, whereas their clinical and cognitive portions were indeed written to be broadly applicable in clinics around the country.
“The clinical and cognitive parts of the AD dementia and MCI criteria are for community use now. But throughout all three sets of criteria, anything that has to do with biomarkers has to be evaluated in research,” Albert told ARF.
Those esteemed readers who missed the hullabaloo may want to grab a cup of coffee and catch up on how the issue played in news reports and in the blogosphere before they read on for a summary of the actual ICAD presentation in Honolulu. Here’s a sampling: One article widely cited as accurate appeared in Medscape Medical News, one that caused head-scratching among scientists, and a slew of angry comments appeared in The New York Times. This was followed by a New York Times Op-Ed. Coverage appeared on ABC News, CBS News, Forbes.com (see also guest reply below the blog), and blogs by clinicians, for example, The Health Care Blog. Some of the coverage prompted Maria Carrillo from the Alzheimer’s Association to clarify the purpose of the draft criteria on CNN. And the Association is holding a media briefing today to do so again.
Resistance against these biomedicine-inspired diagnoses stirred in the psychiatric community, as well, for example, an article in PsychiatricTimes. In an invited independent comment, Allen Frances, professor emeritus at Duke University School of Medicine in Durham, North Carolina, called the guidelines suggested at ICAD a “dreadful mistake”; see comment below. Frances lead the American Psychiatric Division’s DSM-IV task force. In an earlier article about unintended consequences of changing diagnostic criteria in mental illnesses, Frances had similarly critiqued the upcoming DSM-V, which has proposed its own separate set of draft diagnostic guidelines for AD. (If this link pulls up a registration wall, Google “Allen Frances, a warning sign”.) In a response on behalf of the DSM-V’s psychosis group, William Carpenter of the University of Maryland School of Medicine in Baltimore notes, “The field is moving towards early detection, secondary prevention, and more robust therapeutic results,” echoing a similar trend in the AD field.
Taken together, public criticism voiced so far argues against moving toward a pathophysiology-inspired definition of AD in the absence of a cure. But some criticism also comes from the opposite direction. For some researchers in the AD field, the revisions did not go far enough, though most scientists find common ground around the concept that early detection in a research setting is a means towards finding better drugs. For more, see Part 2 and Part 3 of this series.—Gabrielle Strobel.
This is Part 1 of a three-part series. See Part 2 and Part 3.