Alzheimer's Association Plan Calls for Diagnosing the Disease in People with No Memory Problems

In a darkened Amsterdam conference hall this past summer, a panel of industry and academic scientists took the stage to announce a plan to radically expand the definition of Alzheimer’s disease to include millions of people with no memory complaints.

Those with normal cognition who test positive for elevated levels of certain proteins that have been tied to Alzheimer’s — but not proven to cause the disease — would be diagnosed as having Alzheimer’s Stage 1, the panel members explained.

Even before the presentation ended, attendees in the packed hall were lining up behind microphones to ask questions, according to video of the event.

“I’m troubled by this,” Dr. Andrea Bozoki, a University of North Carolina neurologist, told the panel. “You are taking a bunch of people who may never develop dementia or even cognitive impairment and you’re calling them Stage 1. That doesn’t seem to fit.”

Under the proposal, tens of millions of Americans with normal cognition would test positive for abnormal levels of amyloid or tau, the two proteins the tests look for, and the majority of them may never be diagnosed with dementia, studies suggest. A 60-year-old man who tests positive, for example, is estimated to have a 23% risk of developing dementia in his lifetime.

People with no memory problems who test positive would be classified as Stage 1. They would move to Stage 2 if they begin to experience “neurobehavioral difficulties” such as depression, anxiety or apathy — symptoms often unrelated to Alzheimer’s — even if the patient’s cognition is unchanged.

Stage 3 would be for those with mild cognitive impairment, while Stages 4 through 6 would describe patients with mild, moderate or severe dementia.

Pros and cons of proposal

Criticism of the plan has intensified since it was unveiled in July at the international conference attended by 11,000 doctors and scientists, with some calling it premature at best.

“I think this is untested, uncharted territory,” said Dr. Madhav Thambisetty, a senior researcher at the National Institute of Aging. “I’m not at that stage where I would be able to make a diagnosis of Alzheimer’s disease in somebody who’s cognitively normal based on the presence of a single biomarker.”

But the panel, organized by the nonprofit Alzheimer’s Association, is continuing its push to extend the diagnosis to people who have no problem recalling events or what day it is — and convince skeptics that Alzheimer’s symptoms aren’t necessary to have the disease.

Panel members argue that the earlier the patients get help, the more effective it might be. The availability of new drugs for patients with early Alzheimer’s symptoms has spurred them into action now, they say.

The Food and Drug Administration has approved two drugs — Eisai’s Leqembi and Aduhelm from Biogen — for patients in the early stages of memory decline. While a study of Leqembi’s effects on asymptomatic people has begun, there is currently no evidence that giving it to people without cognitive impairment can reduce the risk of dementia or delay the onset of Alzheimer’s symptoms.

Another reason for the change, the panel said, was the availability of new blood tests that do an “excellent” job of detecting abnormal levels of amyloid and tau in the brain. The blood tests are easier and less invasive than the PET scans and spinal taps that traditionally have been used to measure levels of Alzheimer’s-related proteins.

The plan could be approved by the panel and published in a medical journal early this year, association officials said. Such a move is likely to be influential: A similar proposal in 2018 that was put forth to help guide research on experimental Alzheimer’s medications was quickly adopted by the Food and Drug Administration and is frequently cited by doctors, scientists and health insurers.

Financial ties criticized

Standing to benefit are the pharmaceutical and medical testing companies who employ seven members of the 20-person panel. At least seven more members of the panel are academics who receive money from those companies for consulting or research. Panelists said the funding did not influence their decisions.

Four other scientists who are outside advisers to the panel are executives from Eisai and Biogen, the makers of two new medicines for Alzheimer’s patients, and Eli Lilly and Genentech, which are developing similar drugs.

The American Geriatrics Society called the panel members’ financial ties to the industry “wholly inappropriate.” In an analysis of the proposal, the society warned the proposal could lead to overdiagnosis of Alzheimer’s and subject people to treatments with “limited benefit and high potential for harm.”

In its 2023 fiscal year, the Alzheimer’s Association received $4.9 million from pharmaceutical, biotech, diagnostic and clinical research companies — more than in any of the previous five years. The association said those corporate donations amount to just 1.3% of its total cash donations of $379 million that year.

Panel member Maria Carrillo, the association’s chief science officer, said in a statement that “no contribution from any organization impacts the Alzheimer’s Association decision-making, nor our positions.”

“We make our decision based on science, and the needs of our constituents,” she said.