While some are hoping that new diagnostic standards for Alzheimer's represent a much-needed advance, others worry that profits are leading to “diagnostic expansion.”

CNN
—

Another expensive Alzheimer's drug Approval decision The nonprofit Alzheimer's Association will soon release the final version of new diagnostic criteria for Alzheimer's disease. And for the first time, standard They want doctors to diagnose the disease by relying more on biomarkers – fragments of beta-amyloid and tau proteins detected in lab tests and brain scans – rather than pen-and-paper tests of memory and thinking.

The idea behind the change is to catch the disease at its earliest and most treatable stage, before symptoms appear, the authors say, but it also means that Alzheimer's could be diagnosed with just a blood test, even if people don't have memory problems.

The authors argue that biology, not symptoms, should be the basis for diagnosis, and further state that the absence of symptoms does not necessarily mean that symptoms will not develop in the future.

But the standard has been criticized by outside experts and pharmaceutical industry watchdog groups, who point out that beta-amyloid protein can be present in the brain and blood even if a person never shows any symptoms of dementia, and that there's no research to support the idea that giving expensive and dangerous injectable drugs before symptoms appear will benefit patients in the long term.

Risks and benefits of early diagnosis

In clinical trials, the new drug, an antibody that recognizes and traps beta-amyloid debris, removing it from the brain, has shown modest efficacy.

Beta-amyloid peptides are protein fragments that form sticky plaques in the brain and are considered a hallmark of Alzheimer's disease, along with another protein, tau, which forms filamentous tangles that block nerve cell communication.

However, the role of beta-amyloid in the disease remains controversial, with some experts arguing that the plaques are a consequence rather than a cause of the disease.

in 18 months of research In people with the early stages of Alzheimer's disease, treatment with the antibody lecanemab, approved by the U.S. Food and Drug Administration in 2023, slowed the rate of cognitive decline by 27% compared with a placebo.

Also last year, the drug donanemab It seemed to be getting late It slows disease progression by about 35% compared with a placebo. This month, a group of experts who advise the FDA on drug approval decisions unanimously recommended approval of donanemab for Alzheimer's disease.

The drug does carry some risks: As it removes amyloid, it can cause fluid buildup in the brain, swelling and even microbleeds that can lead to hospitalization.

Both studies were conducted on people who showed early symptoms of memory decline. But no symptoms Could not find Benefits for patients.

“There's no evidence to support that,” said Dr. George Perry, a neurobiologist and editor of the Alzheimer's Disease Journal.

Critics say the new standards could dramatically expand the number of people who can get new drugs, generating huge profits for drug companies in the process.

“The Alzheimer's Association should lose all credibility by issuing guidelines that classify completely normal people as having Alzheimer's,” said Dr. Adrienne Hu-Berman, director of PharmaMedOut, a Georgetown University-based program that tracks drug marketing tactics.

“Following these guidelines would ruin the lives of tens of thousands of people who have been misinformed that they have dementia,” she said. “The only people who benefit from this farce are the pharmaceutical companies that make Alzheimer's drugs and the Alzheimer's Association, which preys on fear.”

The Alzheimer's Association says its criteria are based on the latest advances in Alzheimer's science. Because no treatments for Alzheimer's have been approved for people without symptoms, diagnostic tests are not currently recommended for people without cognitive impairment, according to the working group that developed the criteria.

“As the field and our knowledge continue to evolve, our goal in sharing these now is to advance diagnosis, treatment and prevention, improve individual care and reduce the societal impact of Alzheimer's disease,” said Maria C. Carillo, PhD, chief scientific officer and medical affairs officer at the Alzheimer's Association and lead author of the new standards.

The new standards, led by Alzheimer's patient advocacy groups, were developed by a 20-member working group, many of whom reported having financial ties to many of the companies selling or developing new Alzheimer's drugs.

One-third of the expert panel reported being directly employed by pharmaceutical companies, and the other third reported receiving some form of payment from a pharmaceutical or testing company. Two of the panel members are employees of the Alzheimer's Association, which also receives funding from pharmaceutical companies. Only a handful of working group members declared that they had no conflicts of interest.

“We shouldn't rely on this paper, which is basically written by industry. It's not a standard of practice to think about guidelines,” said Dr. Eric Widera, a geriatrician at the University of California, San Francisco, and an author of the paper. Commentary The new criteria are published in the Journal of the American Geriatrics Society.

Widera says this is a familiar tactic for the pharmaceutical industry: expanding the market for a drug by first expanding the population diagnosed with the disease it treats. “It's diagnostic expansion,” he says.

He gives the following example:Is it low T?The “Testosterone” awareness campaign was launched by Abbott Laboratories, the developer of testosterone replacement products and more sensitive hormone tests.

Biogen similarly launched the “It's Time We Know” campaign in 2021 to raise awareness of mild cognitive impairment after its Alzheimer's drug Aduherm received controversial FDA approval that same year. Aduherm was subsequently pulled from the market.

Videla estimates that under the new criteria, one in 10 normally functioning 50-year-olds would test positive for beta-amyloid. 6 million Americans It is estimated that about 40 million people have Alzheimer's disease, but only about 40 million test positive for beta-amyloid.

“Publications like this are an essential part of a strategy aimed at selling as many monoclonal antibodies as possible,” said Dr. Karl Hellup, a professor of neurobiology at the University of Pittsburgh School of Medicine.

Dr. Clifford Jack, a brain imaging researcher at Mayo Clinic, led the development of the new guidelines and said he was proud of the committee's work.

“About 99 percent of the text in the final document was written by me personally, and I have no conflict of interest whatsoever,” he said.

The change in guidelines was prompted by the availability of the first drugs to slow the progression of the disease and new blood tests for amyloid and tau proteins, the authors say. These tests are available to doctors and patients through specialized laboratories that perform them, but they are not approved by the FDA, which will not approve them for widespread use until they have rigorously demonstrated that they do not produce too many false-negative or false-positive results.

in comment Regarding the new standards, published Friday in the journal Nature Medicine, members of the working group said they were made up of members from industry, clinical medicine and academia, as well as the FDA and the federal government's National Institute on Aging, to ensure diverse perspectives.

“We want these standards to reflect the best scientific knowledge currently available, but some of that knowledge is accumulated by the industry that is actually conducting these tests,” Jack said.

“I can honestly say that I have never seen any attempt by committee members to bring any commercial interest into these guidelines,” he said.

The initial draft of the criteria, first presented at the Alzheimer's Association International Conference in 2023, noted that they were being developed in collaboration between the Alzheimer's Association and the National Institute on Aging.

But the new standards drew criticism, and at the request of National Institutes of Health administrators, the institute removed the institute's name from its name. According to an email from the National Institute on Aging, the collaboration violates NIH policy not to endorse private organizations, products, or services.

“NIA continues to participate in the working group and looks forward to continuing its collaboration with the Alzheimer's Association and other interested working group organizations,” the agency said in a statement.

Since the proposed criteria were released, the Alzheimer's Association has clarified that the criteria are not intended to serve as detailed diagnostic guidelines for clinicians. Rather, the criteria are intended to be a “bridge” between research and the physician's office.

The association said it plans to convene a new working group with disparate members to develop “basic” guidelines for doctors on diagnosing Alzheimer's. It is unclear to what extent those guidelines will be based on diagnostic criteria.

“It would have to be very specific and would probably include recommendations describing specific commercial products,” Jack said.

The Alzheimer's Association is committed to developing reliable clinical practice guidelines and “other types of evidence-based guidance that can inform clinical decision-making at the individual, health system and population levels,” spokesman Niles Franz said.

“Core criteria for reliable guidelines as defined by the National Academy of Medicine include collaboration with organizations and panels of clinical and subject matter experts that have minimal intellectual and financial conflicts of interest,” Franz said in a statement.

“To that end, the association has recently established rules regarding collections. [conflict of interest] “Disclosures from guideline panel candidates, the criteria for evaluating these forms and selecting panel members, and the process for managing existing and new conflicts of interest during and after the development of the guidelines,” he said.

Franz said the association hopes to have new clinical guidelines available to publish by 2025.

Meanwhile, Widera and his colleagues say the decision about whether to take one of the new amyloid-clearing drugs is a highly personal one that should be made in close collaboration with a doctor.

“There's probably more controversy surrounding these guidelines than the drugs themselves,” Widera said.

Videla said he hopes the Alzheimer's Association will consider the associated risks in its next set of guidelines.

“If we are going to broaden the definition of disease, we should also state the risks and harms of doing so,” he said.