Should Alzheimer's be diagnosed without symptoms? Proposal to use blood tests causes excitement among scientists

Should Alzheimer's be diagnosed without symptoms? Proposal to use blood tests causes excitement among scientists

A controversy about the attempt has arisen among researchers Blood tests and brain scans to diagnose Alzheimer's disease To introduce instead of the cognitive tests that have been used for decades.

Proponents of this change argue that new biomarker tests Alzheimer's can recognize at a very early stage- the best time to apply treatments to the return of the disease. But critics point out that this well-intentioned initiative could lead to people being diagnosed on a single test even if they don't show symptoms of cognitive decline — and may never develop any.

"There is a risk that asymptomatic people will experience incomprehension and stress if we tell them they have Alzheimer's. But in most cases, nothing will happen in their lives," says Nicolas Villain, a neurologist at Sorbonne University in Paris, who wrote a paper published Nov. 1 in JAMA Neurology 1 wrote down and criticized the new diagnostic criteria.

Plaques and complications

The brains of people with Alzheimer's have two key characteristics: Plaques of sticky amyloid-β proteins and tangles of tau proteins. The neurodegeneration associated with the development of these plaques and tangles is irreversible, which is why researchers are seeking treatments to help healthy people completely avert this damage.

In recent years, companies have started To market drugs that slow cognitive decline in Alzheimer's disease by removing amyloid from the brain, and scientists have highly accurate assays for both amyloid and tau proteins perfected.

"This union is the possibility of a widespread, clinically available precise diagnosis with the possibility of doing something against the disease that has caused us to update the criteria," says Clifford Jack, specialist for clinical Alzheimer's and dementia research at Mayo Clinic in Rochester, Minnesota, which was involved in overworking the diagnosis criteria. Jack and his colleagues in a working group of the Alzheimer's Association, a non-profit research and interest group in Chicago, Illinois, published their guidelines in June 2 In the magazine Alzheimer’s & Dementia.

The criteria stated that a single abnormal result in a core set of biomarker -based tests is sufficient to diagnose Alzheimer's. These tests include Measurements of amyloid and tau protein levels in the blood or cerebrospinal fluid, as well as positron emission tomography (PET), which helps quantify amyloid plaques.

Devastating diagnosis

But Villain and his colleagues point out in their critique that a large proportion of people diagnosed this way would never develop cognitive symptoms: A 65-year-old man who is amyloid biomarker positive has a lifetime risk of about 22% for developing Alzheimer's dementia, which is only about 1.7 times higher than the risk for a similar person who is is amyloid biomarker negative.

The critics also argue that people who are tested positively for a single biomarker and are cognitively unaffected should be informed that they have a risk of the disease, but should not receive any official Alzheimer's diagnosis. A person without symptoms who are either tested positively in several biomarker tests or A gene variant has significantly increased the risk of developing Alzheimer's dementia, could be classified as a “presymptomatic” Alzheimer’s diagnosis, the critics write.

Jack acknowledges that biomarker tests make it possible to diagnose asymptomatic people with the disease-however, the guidelines say that biologically based diagnoses are intended to "support, but not to replace". And the working group does not recommend Alzheimer's biomarker tests for healthy people, so that hypothetical positive diagnosis for someone without symptoms should not occur, he says.

Still, the new criteria could expand eligibility for clinical trials that could help develop treatments for asymptomatic people, Jack said. “The reality is that every person who ultimately becomes demented due to Alzheimer's has been asymptomatic with the disease for a period of time,” he says. “In the future, medicine needs to focus on how to prevent the onset of symptoms, because by the time someone becomes symptomatic, extensive irreversible damage has already occurred.”

Nothing on the shelf

Currently, medications for biomarker-positive, asymptomatic individuals are lacking except in clinical trials, says Andrea Bozoki, a cognitive neurologist at the University of North Carolina School of Medicine at Chapel Hill who co-authored the JAMA Neurology review. This would leave such individuals with the psychological pain of having a diagnosis of a terminal illness but no treatment options, she says.

The new drugs that slow the cognitive decline caused by the disease, are only approved in the United States for people who already suffer from mild cognitive impairment.

Bozoki fears the new criteria will encourage healthy people who fear they are at risk or who have a family history of the disease to see a doctor who will order a biomarker test for them. If they are diagnosed, she says, they could be prescribed the new Alzheimer's drugs. These have not been shown to be effective in asymptomatic groups, cost tens of thousands of dollars per year and carry the risk of cerebral hemorrhage and fatal seizures.

That will make it even more important that researchers and doctors ensure they properly communicate risks and uncertainties as Alzheimer's tests and drugs become more accessible, said Winston Chiong, a neurologist and ethicist at the University of California, San Francisco, who was not involved in any of the working groups.

1. Dubois, B. et al. JAMA Neurol. https://doi.org/10.1001/jamaneurol.2024.3770 (2024).

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2. Jack, C. R. et al. Alzheimer. Dement. https://doi.org/10.1002/alz.13859 (2024).

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