Should Alzheimer’s disease be diagnosed without symptoms? Proposal to rely on blood tests worries scientists

There has been controversy among researchers over the attempt to take blood tests and brain scans to diagnose Alzheimer’s diseaserather than the cognitive screening that has been used for decades.

Supporters of the changes say new biomarker tests could detect Alzheimer’s disease at a very early stage. is the best time to use any treatment developed to reverse the disease.. But critics say that while these efforts are well-intentioned, it means people can be diagnosed with a single test even if they don’t have symptoms of cognitive decline – and may never develop them.

“There is a risk of misunderstanding and suffering that can occur in people who have no symptoms if we tell them they have Alzheimer’s disease, when in most cases nothing will happen in their lives,” says Nicolas Villan, a neurologist at the University Sorbonne in Paris, who co-authored the article¹ published November 1st in JAMA Neurology criticizing new diagnostic criteria.

Plaques and tangles

The brains of people with Alzheimer’s disease have two key features: plaques of sticky β-amyloid proteins and tangles formed from tau proteins. The neurodegeneration associated with the development of these plaques and tangles is irreversible, so researchers are looking for treatments that can be given to healthy people to completely prevent this damage.

In the last few years, companies have begun to sell drugs that slow cognitive decline associated with Alzheimer’s disease by clearing amyloid from the brainand scientists are improving highly accurate tests for amyloid and tau protein.

Researchers are calling for a major rethink of how treatments for Alzheimer’s disease are evaluated.

“It was this combination of the possibility of widespread, clinically accessible and accurate diagnosis with the ability to do something about the disease that prompted us to update the criteria,” says Clifford Jack, a clinical researcher in Alzheimer’s disease and dementia at the Mayo Clinic in Rochester. Minnesota, who led efforts to revise diagnostic criteria. Jack and his colleagues on a working group for the Alzheimer’s Association, a nonprofit research and advocacy organization in Chicago, Illinois, published their recommendations.² in the magazine Alzheimer’s disease and dementia in June.

The criteria state that any abnormal result on a core battery of biomarker-based tests is sufficient to diagnose Alzheimer’s disease. These tests include measuring amyloid and tau protein levels in the blood or cerebrospinal fluid, and positron emission tomography (PET) scans of the brain, which help quantify amyloid plaques.

A devastating diagnosis

But Willen and his colleagues note in their critique that a large group of people with this diagnosis will never develop any cognitive symptoms: a 65-year-old man with a positive amyloid biomarker has a risk of developing Alzheimer’s dementia of about 22%, only about 1 .7 times higher than the risk for a similar person with a negative amyloid biomarker.

Critics also argue that people who test positive for one biomarker and without cognitive impairment should be informed that they are at risk for the disease, but should not receive a formal diagnosis of Alzheimer’s disease. An asymptomatic person who either tests positive for multiple biomarkers or has a gene variant that is known to significantly increase the risk of developing Alzheimer’s dementia. could be diagnosed as “pre-symptomatic” Alzheimer’s disease, critics write.

Alzheimer’s drug approval baffles research community

Jack acknowledges that biomarker testing can diagnose disease in asymptomatic people, but the guidelines say biological diagnoses are meant to “assist, not replace” clinical assessments. The task force does not recommend testing for biomarkers of Alzheimer’s disease in healthy people, so a hypothetical positive diagnosis for an asymptomatic person should not come true, he says.

However, the new criteria could expand eligibility for clinical trials, which could help develop treatments for asymptomatic people, Jack says. “The reality is that every person who eventually becomes dementia due to Alzheimer’s disease has gone through a period of time when the disease was asymptomatic,” he says. “Medicine must focus its future on how to prevent symptoms from occurring, because by the time someone develops symptoms, extensive, irreversible damage has already been done.”

There’s nothing in the closet

But there is currently no cure for people with positive biomarkers and no symptoms, except in clinical trials, says Andrea Bozocki, a cognitive neurologist at the University of North Carolina School of Medicine at Chapel Hill and co-author of the study. JAMA Neurology criticism. She said this would result in such people experiencing mental anguish due to a diagnosis of a terminal illness but lack of treatment options.

new drugs that slow cognitive decline caused by the disease Approved in the US only for people who already experience mild cognitive impairment.

Bozoki worries that the new criteria will push healthy people who fear they are at risk of developing Alzheimer’s disease, or who have a family history of the disease, to seek out a doctor who will prescribe a biomarker test for them. And if they are diagnosed, she says, they may be prescribed new drugs for Alzheimer’s disease. Their effectiveness in asymptomatic populations has not been proven. cost tens of thousands of US dollars per year and carry the risk of brain hemorrhage. and fatal seizures.

That will make it even more important for researchers and doctors to ensure that risks and uncertainties are properly communicated as tests and drugs for Alzheimer’s disease become more available, says Winston Chiong, a neurologist and ethicist at the University of California, San Francisco, who was not involved. in any work group.