Experts want to diagnose Alzheimer’s with a test – 03/16/2024 – Equilíbrio

Determining whether someone has Alzheimer’s disease often requires a prolonged diagnostic process. A doctor reviews a patient’s medical history, discusses symptoms, and administers verbal and visual cognitive tests.

The patient may undergo a positron emission tomography (PET scan), a magnetic resonance imaging (MRI) or a lumbar puncture — tests that detect the presence of two proteins in the brain, amyloid plaques and tau tangles, both associated with Alzheimer’s. .

But all that could change if new criteria proposed by an Alzheimer’s Association working group are widely adopted.

Its final recommendations, expected later this year, will accelerate a shift that is already underway: from defining disease by symptoms and behavior to defining it purely biologically — with biomarkers, substances in the body that indicate the disease.

The draft guidelines, Revised Criteria for the Diagnosis and Staging of Alzheimer’s Disease, call for a simpler approach. This could mean a blood test to indicate the presence of amyloid [a proteína beta-amilóide, que forma placas no cérebro na doença de Alzheimer]. Such tests are already available in some clinics and doctors’ offices.

“Someone who has evidence of amyloid biomarkers in the brain has the disease, whether they are symptomatic or not,” says Clifford R. Jack Jr., chairman of the working group and an Alzheimer’s researcher at the Mayo Clinic.

“The pathology exists years before the onset of symptoms,” he added. “That’s the science. It’s irrefutable.”

He and his colleagues on the panel do not recommend testing people who do not have symptoms of cognitive decline. But skeptics predict it will likely happen anyway. If this occurs, a considerable proportion would test positive for amyloid and therefore be diagnosed with Alzheimer’s.

A 2015 Dutch study estimated that more than 10% of cognitively normal 50-year-olds would test positive, as would nearly 16% of 60-year-olds and 23% of 70-year-olds. Most of these individuals would never develop dementia.

Several experts and stakeholders remain unconvinced by the argument for turning to biomarkers alone, however. The American Geriatrics Society called the proposed criteria “premature” — and noted the high proportion of panel members with ties to the pharmaceutical and biotechnology industries, creating potential conflicts of interest.

“This is being rushed for at least five to 10 years,” says Eric Widera, a geriatrician at the University of California, San Francisco, and author of a sharply critical editorial in the Journal of the American Geriatrics Society.

Some background: The panel undertook the effort just five years after issuing the last diagnostic guidelines because “two major events really necessitated a review,” Jack said.

First, the best of the blood tests for amyloid have proven to be highly accurate, less invasive than spinal taps, and much less expensive than brain scans. Additionally, aducanumab (brand name: Aduhelm) and lecanemab (Leqembi), two drugs that remove amyloid from the brain, have received regulatory approval, although not without intense controversy.

Studies showed that the drugs had a modest but statistically significant ability to slow the progression of symptoms over 18 months in people with mild cognitive impairment or mild Alzheimer’s disease. (Drug maker Biogen is withdrawing aducanumab, but other amyloid-lowering drugs are in development.)

Are these developments enough to justify diagnosing healthy people with an irreversible disease based on a blood test that detects amyloid? Some doctors are already receiving such requests.

Diagnosing Alzheimer’s before symptoms appear could allow as-yet-undeveloped treatments to prevent the memory loss, impaired judgment and eventual dependence that the disease causes. Doctors diagnose many diseases, including diabetes and cancer, with tests on asymptomatic people.

But how many of those with amyloid in the brain (most of whom will also have tau deposits) will eventually develop dementia? “The answer, unfortunately, is that it depends,” Jack said.

The Mayo Clinic Study of Aging followed nearly 5,000 cognitively normal older adults in one Minnesota county for an average of 9.4 years. He found high rates of dementia among those who carried the APOE4 gene, which is associated with an increased risk of Alzheimer’s.

For those who were 65 years old and had high amyloid levels, the estimated lifetime risk of dementia reached 74% for women and 62% for men.

But only 15% to 25% of people carry this gene, according to the National Institute on Aging. Among participants who didn’t have it, both men and women at age 65 had an estimated lifetime risk of dementia of about 55% with high amyloid levels and 36% with moderate levels.

“Because mortality rates are high in older people, many will die before developing dementia,” says

Jason Karlawish, a geriatrician and co-director of the Penn Memory Center in Philadelphia, said he considers amyloid “a risk factor in the same way that smoking is a risk factor for cancer,” adding, “but I think the evidence It is still not clear and convincing that amyloid alone defines Alzheimer’s disease.”

Two important studies of amyloid-lowering drugs in cognitively normal people, expected to be completed in 2027 and 2029, could provide this evidence if they can demonstrate that removing amyloid prevents, halts, or reverses cognitive decline in this age group.

For now, the proposed guidelines “are simply not ready for clinical practice,” Karlawish said.

As for the working group, around a third of the 22 members are employed by companies that develop medicines and diagnostics, according to their disclosures. Approximately another third disclose research grants or contracts, consulting fees, honoraria, or other payments from industry sources.

“They will directly benefit from this change,” Widera said. He pointed to estimates that 40 million cognitively normal Americans could test positive for amyloid, be diagnosed with Alzheimer’s disease and possibly begin off-label drug regimens, despite there being no evidence to date that the drugs are effective in asymptomatic people. .

“These are not harmless medicines,” Widera added. “You will be on these medications for the rest of your life — like a statin, but much more expensive and much more dangerous.”

Aducanumab and lecanemab can cause brain bleeding and reduced brain volume, side effects that are not uncommon.

Widera further criticized the working group’s proposal for not discussing the harms of the new criteria — including needlessly terrorizing people unlikely to develop dementia and potentially causing discrimination in employment and insurance.

Jack, who has no reported conflicts of interest, defended his working group. “Members are committed to accurately reflecting what current science says,” he said. “There was no consideration of commercial gain. Everyone was focused on what’s best for patients.”

However, numerous studies have found that industry payments and sponsorships, even for cheap meals, have measurable influence. They are associated with doctors being more likely to prescribe promoted drugs and with more favorable research outcomes when manufacturers sponsor studies of drugs and medical devices.

Many patient advocacy groups, including the Alzheimer’s Association, also have ties to the industry.

Often, redefining diseases or revising guidelines means lowering thresholds and broadening classifications, sometimes called “diagnostic creep.” The thresholds for high blood pressure and high cholesterol are lower now than in previous years, for example. New precursor conditions, such as prediabetes, also expand the number of people defined as having a disease.

With amyloid testing as the criteria, “there will be a new pandemic of Alzheimer’s disease,” Widera predicted. “There will be a big push for early detection.”

Part of that push may come from patients themselves. “We’re in an information age where people are interested in knowing more about their current and future health,” says Gil Rabinovici, a neurologist who directs the Alzheimer’s Disease Research Center at the University of California, San Francisco.