The National Institute on Aging and the Alzheimer’s Association have proposed revised clinical guidelines that would designate seven major stages of the brain disease. The first two would be for people who have no symptoms but may be at higher risk for Alzheimer’s.

These technical guidelines, which would update a 2018 version, could have enormous, and conflicting, implications for drug research, health care costs, access to insurance, and the psychological well-being of older adults.

At almost the same time, Quest Diagnostics announced it has begun selling a $399 home test that it claims will show consumers if they are at risk for developing Alzheimer’s. While the benefits remain unproven, it raises many of the same issues.

Costs And Benefits

Proponents argue that new guidelines and tests could provide early warning to those who may be likely to develop cognitive impairment in the future. That could lead them to proactive interventions, which could delay or ease future symptoms. And many researchers believe anti-Alzheimer’s drugs are most effective if administered even before the disease begins to damage the brain.

But the value of many of today’s treatments is unclear at best. More troubling, many patients who never will develop symptoms would have to live with the consequences of an Alzheimer’s diagnosis for the rest of their lives.

There will be some unambiguous winners. Drug researchers and drug makers as well as advocacy groups such as the Alzheimer’s Association will be able to say that millions more people “have” the disease. That inevitably will mean more government funding. And if Alzheimer’s screenings ever become a standard part of, say, annual checkups for those age 65 and older, the new guidelines could become a massive windfall for testing companies at great cost to Medicare.

Of the 22 members of the panel that developed the guidelines, 16 either work for or have received consulting fees or research grants from the Alzheimer’s Association or from drugmakers. There were only two independent researchers, and no representatives of people living with Alzheimer’s, their families, or consumer groups.

The proposed stages would reflect people:

  • Stage 0: Who carry the gene APOE4 that makes Alzheimer’s more likely but show no symptoms or evidence of a build-up of proteins amyloid beta or tau in their brains.
  • Stage 1: With unusually high levels of amyloid beta or tau but no cognitive decline.
  • Stage 2: With normal cognitive test results but some recent decline in function or mood.
  • Stage 3: With the ability to perform daily activities but who show increasing functional decline.
  • Stage 4: With mild functional impairment.
  • Stage 5 With moderate functional impairment and more difficulty managing daily activities.
  • Stage 6: With severe functional impairment.

What makes the guidelines so controversial? In part it is because not everyone who carries the gene APOE4 will get Alzheimer’s and many people who do have the disease do not have the gene. Similarly, while amyloid beta and tau are associated with Alzheimer’s the evidence that they cause Alzheimer’s remains ambiguous. And some people with significant amount of these proteins in their brains never develop any cognitive impairment.

Effects On Research

While these stages are described as clinical guidelines, they would make it far easier for researchers to enroll people with no memory loss or cognitive impairment in drug trials. And they would vastly increase the number of people diagnosed with Alzheimer’s, a potential boon for funding for both the researchers and advocacy groups, as well as the companies that make the tests and the treatments.

Yet enrolling people in trials before they have any disease is highly controversial and, in the minds of some, unethical. It is especially fraught when the drugs being tested have potentially dangerous side effects. For example, Leqembi, the drug just approved by the FDA, caused brain bleeds and swelling in many trial participants. In three cases, the bleeding was fatal.

But if someone can be diagnosed with Stage 0 or Stage 1 Alzheimer’s, enrolling them in a trial may be less controversial. Determining whether people are at higher risk for the disease requires testing—a blood test for the gene but generally a PET scan or spinal tap for the presence of the proteins. These tests are costly and not without risks themselves. And they raise a critical question; Do you want to know?

Increasing Anxiety

Many older adults are terrified about developing dementia. What will it do to their self-image and ability to function if they get a diagnosis of a disease such as Alzheimer’s, even when they have no symptoms? And when there are no clearly beneficial treatments?

Will it cause anxiety or depression? How will it affect their relationships with family? Will they be refused long-term care insurance coverage or limited in their ability to switch Medicare Supplement (Medigap) insurers? Will they become susceptible to pitches for phony cures?

It would be easy to support these revised clinical guidelines if the costs and benefits were unambiguous. But like so much with Alzheimer’s, they are not.