Free of Memory Problems, but Diagnosed With Alzheimer’s?

March 20, 2024

Can someone who has no memory problems be given a diagnosis of Alzheimer’s disease?

That is the conundrum posed by proposed new guidelines that seek to change the definition of who has Alzheimer’s disease. The draft guidelines, led by a workgroup of experts assembled by the Alzheimer’s Association, would dramatically expand the number of people with Alzheimer’s, including millions who have no memory complaints or thinking problems. Many of them would never go on to develop what doctors currently consider dementia or mild cognitive impairment, the serious memory problems that can progress to full-blown Alzheimer’s.

Under the proposal, people without memory problems but who have abnormal levels of toxic beta-amyloid in the brain would be defined as having stage 1 Alzheimer’s disease. The presence of beta-amyloid, which in its toxic form clumps together to form plaques in the brain, is a hallmark of Alzheimer’s disease. The abnormal accumulation of beta-amyloid is increasingly easy to detect using blood tests and brain scans. But beta-amyloid can begin to accumulate decades before memory loss and other symptoms become apparent. And many people with abnormal accumulations of the toxic protein will never go on to develop serious memory problems or Alzheimer’s disease as we know it today.

According to the proposed guidelines, later stages of Alzheimer’s would be defined by the development of behavioral symptoms, such as apathy or depression; the development of mild cognitive impairment, or MCI; and, finally, the serious memory loss, thinking deficits and behavioral changes of mild, moderate and advanced dementia.

Proponents of the guidelines argue that early detection of Alzheimer’s, through blood tests and/or brain scans, would allow for early treatments that could potentially delay the onset of memory loss and other symptoms. Many of the newer drugs for Alzheimer’s, such as Leqembi, target beta-amyloid in the brain, and some experts believe the earlier the drugs are given in the course of Alzheimer’s, the more effective they may be. 

But whether beta-amyloid accumulation leads directly to symptom progression remains unproven, and critics of the guidelines argue that diagnosing and treating the disease five, 10 or even 20 years before memory loss appears would potentially expose patients to potentially harmful side effects from drugs they may never need. The drugs are very expensive and have been known to cause brain swelling and bleeding, and in some cases may even prove fatal.

In a recent commentary in the Journal of the American Geriatrics Society, Dr. Eric Widera of the University of California, San Francisco, notes that some 40 million cognitively normal Americans would currently test positive for beta-amyloid. “A cognitively normal 50-year-old would have a 1 in 10 chance of being amyloid positive,” he notes. “Furthermore, it would be a stretch to call this new definition of Alzheimer’s disease a progressive disease as most of these individuals will never progress to either MCI or dementia during their lifetimes.” Other studies indicate that a 60-year-old man who tests positive for beta-amyloid, for example, would have less than a one in four chance of ultimately developing dementia in his lifetime.

The American Geriatrics Society and other professional groups say the guidelines are premature and point out that many members of the guidelines panel have financial ties to pharmaceutical companies that make the drugs or medical testing companies that monitor patients taking the drugs. Giving a healthy patient a diagnosis of Alzheimer’s can also raise the risk of depression or anxiety and raises ethical questions about whether certain employees who get tested, such as airline pilots, must disclose the results to their employers. 

The guidelines are only a draft proposal, and it is uncertain whether they will be adopted by medical groups. In the meantime, debate continues.

You can learn more about the proposed guidelines and the fascinating issues they raise in:

“Inside the Plan to Diagnose Alzheimer’s in People With No Memory Problems—and Who Stands to Benefit,” by Melody Petersen, The Los Angeles Times, February 14: https://www.latimes.com/science/story/2024-02-14/inside-controversial-plan-to-diagnose-alzheimers-in-people-without-symptoms

“Apparently Healthy, But Diagnosed With Alzheimer’s?” by Paula Span, The New York Times, March 4: https://www.nytimes.com/2024/03/04/health/alzheimers-amyloid-diagnosis.html

By ALZinfo.org, The Alzheimer’s Information Site. Reviewed by Eric Schmidt, Ph.D., Fisher Center for Alzheimer’s Research Foundation at The Rockefeller University. 

Sources: Eric Widera: “Who Gets to Decide on What It Means to Have Alzhemer’s Disease?” Journal of the American Geriatrics Society, February 12, 2024

“Revised Criteria for Diagnosis and Staging of Alzheimer’s Disease: Alzheimer’s Association Workgroup.” October 2023, https://aaic.alz.org/diagnostic-criteria.asp


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