Apparently healthy, but diagnosed with Alzheimer’s disease?

Determining whether someone has Alzheimer’s disease usually requires an extensive diagnostic process. A doctor takes a patient’s medical history, discusses symptoms, and administers verbal and visual cognitive tests.

The patient may undergo a PET scan, an MRI or a spinal tap – tests that detect the presence of two proteins in the brain, amyloid plaques and tau tangles, both associated with Alzheimer’s disease.

All this could change dramatically if the new criteria, proposed by a working group of the Alzheimer’s Association, become widely accepted.

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

The design guidelines, Revised criteria for diagnosis and staging of Alzheimer’s disease, argues for a simpler approach. That could mean a blood test to show the presence of amyloid. Such tests are already available in some clinics and doctors’ offices.

“Someone with biomarkers that show amyloid is present in the brain has the disease, whether it is symptomatic or not,” said Dr. Clifford R. Jack Jr., chair of the task force and a researcher in the disease field. Alzheimer’s at the Mayo Clinic.

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

He and his colleagues on the panel recommend against testing people who have no symptoms of cognitive decline. But skeptics predict this is likely to happen anyway. If so, a significant proportion would test positive for amyloid and therefore be diagnosed with Alzheimer’s.

a 2015 Dutch study It is estimated that more than 10 percent of cognitively normal 50-year-olds would test positive, as would almost 16 percent of 60-year-olds and 23 percent of 70-year-olds. Most of these people would never develop dementia.

A number of experts and interested parties however, remain unconvinced by the argument for turning to biomarkers alone. The American Geriatrics Society has done just that called the proposed criteria “premature” – and pointed out the high percentage of panel members with ties to the pharmaceutical and biotechnology industries, creating potential conflicts of interest.

“This is a leap forward of at least five to ten years,” says Dr. Eric Widera, a geriatrician at the University of California, San Francisco, and author of a sharply critical book. editorial in the Journal of the American Geriatrics Society.

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

First, the best amyloid blood tests proved to be highly accurate, less invasive than spinal taps and much cheaper than brain scans. In addition, aducanumab (brand name: Aduhelm) and lecanemab (Leqembi), two drugs that remove amyloid from the brain, received regulatory approval, but not without intense controversy.

Research has shown that the drugs have a modest but statistically significant ability to slow the progression of symptoms for 18 months in people with mild cognitive impairment or mild Alzheimer’s disease. (The drugmaker Biogen is withdrawing aducanumab, but other amyloid-reducing drugs are in the pipeline.)

Are these developments enough to justify the possibility of diagnosing healthy people with irreversible disease, based on a blood test that detects amyloid? Some doctors have already made such requests.

Diagnosing Alzheimer’s disease before symptoms emerge could enable yet-to-be-developed treatments to prevent the memory loss, impaired judgment and eventual dependency 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,” said Dr. Jack.

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

For those who were 65 and had high amyloid levels, the estimated lifetime risk of dementia was 74 percent for women and 62 percent for men.

But only 15 to 25 percent of people carry that gene, according to the National Institute on Aging. Among participants who did not, both men and women aged 65 years had an estimated risk of dementia of about 55 percent at high amyloid levels and 36 percent at moderate levels.

“Because mortality rates among the elderly are high, many will die before developing dementia,” said Dr. Jack.

Dr. Jason Karlawish, a geriatrician and co-director of the Penn Memory Center in Philadelphia, said he considers amyloid a risk factor, just as smoking is a risk factor for cancer.

“But I think the evidence is still not clear and convincing that amyloid alone defines Alzheimer’s disease.”

Two large trials of amyloid-reducing drugs in cognitively normal people, expected to be completed in 2027 and 2029, could provide such evidence if they can show that removing amyloid prevents, halts or reverses cognitive decline in that age group.

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

As regards the working groupAbout a third of the 22 members work at companies that develop drugs and diagnostics, according to their disclosures. About another third disclose research grants or contracts, consulting fees, honoraria, or other payments from industry sources.

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

“These are not benign drugs,” added Dr. Widera added. “You will have to take these drugs for the rest of your life – just like a statin, but much more expensive and much more dangerous.” Aducanumab and lecanemab can cause brain hemorrhages and reduce brain volume, side effects that are not uncommon.

Dr. Widera further criticized the working group’s proposal not to discuss the harms of the new criteria – including unnecessarily frightening people who are unlikely to develop dementia and potentially causing discrimination in employment and insurance.

Dr. Jack, who has reported no conflicts of interest, defended his working group. “The members are committed to accurately representing what current science says,” he said. “No commercial gain was taken into account. Everyone was focused on what is best for the patients.”

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

A lot of patient advocacy groupsincluding the Alzheimer’s Association, also have ties to the industry.

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

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

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

Early diagnosis of Alzheimer’s disease could lead to lifestyle changes — quitting smoking, exercising, improving diet — that could still have “a protective effect,” he said.

“Personally, I wouldn’t want to know if I had plaques in my brain,” he added. And he wouldn’t prescribe amyloid drugs to patients without symptoms, he said, until further research showed effectiveness in that cohort.

Still, we have “moved away from the idea that the doctor decides who learns what,” he said, adding that after thorough counseling “if I am convinced that I am not going to harm them and I feel that they can get the information understand what they get’. I’m not going to refuse to offer them a test.”