Seemingly healthy, but diagnosed with Alzheimer’s?

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

The patient may undergo a PET scan, an 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.

That could all change dramatically if new criteria proposed by an Alzheimer’s Association task force are widely adopted.

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

The draft guidelines, Revised criteria for the diagnosis and staging of Alzheimer’s disease, demand a simpler approach. That could mean a blood test to indicate the presence of amyloid. These tests are now available in some clinics and doctors’ offices.

“Someone who has evidence of amyloid biomarkers in the brain has the disease, whether symptomatic or not,” said Dr. Clifford R. Jack Jr., chair of the task force and an Alzheimer’s researcher at the Mayo Clinic.

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

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

TO Dutch study from 2015 It was estimated that more than 10 percent of cognitively normal 50-year-olds would test positive, as would nearly 16 percent of 60-year-olds and 23 percent of 70-year-olds. Most of those people would never develop dementia.

Various experts and concerned parties However, we are not convinced by the argument in favor of relying solely on biomarkers. The American Geriatrics Society has described the proposed criteria as “premature” – and has noted the high proportion of panel members with ties to the pharmaceutical and biotech industries, creating potential conflicts of interest.

“This is at least five to 10 years ahead of time,” said Dr. Eric Widera, a geriatrician at the University of California, San Francisco, and author of a highly critical paper. editorial in the Journal of the American Geriatrics Society.

Some background: The panel undertook the effort only five years after issuing the last diagnostic guidelines, because “two big events really called for a review,” Dr. Jack said.

First, the best blood test for amyloid turned out 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 clear amyloid from the brain, received regulatory approval, although not without intense controversy.

The studies showed that the medications had 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. (Drug maker Biogen is withdrawing aducanumab, but other amyloid-lowering drugs are in the works.)

Are these advances enough to justify the possibility of diagnosing healthy people with an irreversible disease based on a blood test that detects amyloid? Some doctors are already responding to requests of this type.

Diagnosing Alzheimer’s before symptoms arise could allow for yet-to-be-developed treatments to prevent the memory loss, decreased judgment and eventual dependency that the disease causes. Doctors diagnose many diseases, including diabetes and cancer, by testing asymptomatic people.

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

He Mayo Clinic Aging Study They followed nearly 5,000 cognitively normal older adults in one 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.

For those who were 65 years old and had high amyloid levels, the estimated lifetime risk of dementia reached 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 had an estimated lifetime risk of dementia of about 55 percent with high levels of amyloid and 36 percent with moderate levels.

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

Dr. 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.

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

Two major studies of amyloid-lowering drugs in cognitively normal people, expected to conclude in 2027 and 2029, could provide such evidence if they are able to show that amyloid removal prevents, stops or reverses cognitive decline in that age group.

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

as for the working group, about a third of the 22 members are employed at companies that develop drugs and diagnostics, their disclosures show. Approximately another third discloses research grants or contracts, consulting fees, honoraria or other payments from industry sources.

“They will directly benefit from this change,” Dr. 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 start unapproved drug regimens, even though there is no evidence to date that the drugs are effective in asymptomatic people.

“These are not benign medications,” Dr. Widera added. “You’ll be taking these drugs for the rest of your life, 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 task force’s proposal for failing to discuss the harms of the new criteria, including needlessly terrorizing people unlikely to develop dementia and potentially causing discrimination in employment and insurance.

Dr. Jack, for whom no conflicts of interest have been reported, defended his working group. “Members are committed to accurately reflecting what current science says,” he said. “No commercial gain was considered. “Everyone focused on what is best for the patients.”

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

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

Often, redefine diseases or review guidelines It means lowering thresholds and expanding classifications, sometimes called “diagnostic advancement.” The thresholds for high blood pressure and high cholesterol are now lower than in previous years, for example. New precursor conditions, such as prediabetes, also expand the number of people suffering from a disease.

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

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

An early diagnosis of Alzheimer’s disease could prompt lifestyle changes (stopping smoking, exercising, improving diet) that could still have “a protective effect,” he said.

“I personally wouldn’t choose to know if I have plaques in my brain,” he added. And he wouldn’t prescribe amyloid drugs to patients without symptoms, he said, until more research shows efficacy in that cohort.

Still, “we have graduated from the notion that the doctor determines who learns what,” he said, adding that after extensive counseling, “if I am convinced that I am not going to harm them and I feel that they understand the information they are receiving , “I’m going to get it, I’m not going to refuse to offer you a test.”