Diagnosing alzheimer’s in people with no symptoms

That’s in large part because the medications that reduce levels of amyloid in the brain — Leqembi (lecanemab) and Kisunla (donanemab) — have only shown benefits in people with mild cognitive

impairment (MCI) or mild-stage dementia, and their potential side effects can be serious. To date, “we have zero evidence … that treating people with just amyloid in their brain leads to

any positive outcome,” says Eric Widera, M.D., professor of medicine and clinician-educator in geriatric medicine at the University of California, San Francisco (UCSF). Those studies, called

AHEAD and TRAILBLAZER-ALZ 3, described below, are happening now. Widera is a member of the International Working Group, or IWG, researchers from 17 countries who published a 2024 paper in

_JAMA Neurology_ cautioning against diagnosing people with Alzheimer’s disease based solely on biology without signs of dementia. The IWG and others warn that the availability of blood tests

can cause undue worry for people who test positive without getting appropriate counseling on how to interpret the results. “They’ll be confused because they’ll know they don’t have

Alzheimer’s dementia … but they’ll start to notice every problem with their memory,” says Deborah Blacker, M.D., geriatric psychiatrist and epidemiologist at Massachusetts General Hospital.

In reality, not every memory blip is cause for concern; some are due to inattentiveness (you lost your keys because you were distracted when you walked in the door), or lack of sleep or even

certain medications. Importantly, most people with amyloid in their brain make it through life free of dementia. Having tau in the brain increases risk, but not to 100 percent. In a 2018

computer modeling study that estimated probabilities of disease progression based on amyloid status and other factors such as age and national death rates, fewer than 1 in 4 cognitively

normal 75-year-old women who test positive for amyloid go on to develop Alzheimer’s dementia during their lifetime. For men at the same age, that figure is 1 in 5. It’s been known for

decades that many who die with normal cognition have “a head full of amyloid,” Blacker says. For a 75-year-old woman with both amyloid and tau in her brain, the lifetime risk of Alzheimer’s

dementia is closer to 1 in 3. “There’s a lot that needs to go wrong for something as important as cognition to fail,” adds Fanny Elahi, M.D., a neurologist-scientist at the Icahn School of

Medicine at Mount Sinai in New York City. “We actually are very resilient.” TEST RESULTS MAY CAUSE UNNECESSARY ALARM When people hear “Alzheimer’s disease,” most imagine the dreadful

condition that robs a person’s memory and thinking skills — not an abnormal test result. A blood test measures biology, Elahi says. “It doesn’t equate to dementia. It doesn’t mean [those

testing positive] are ‘doomed.’ ” Still, the psychological impact of biomarker tests on people with no apparent impairment is murky. Some worry that disclosing test results may invite

possible discrimination in employment, housing and insurance. But since “we know there is biology that contributes to Alzheimer’s-related dementia,” she adds, a test tells someone they are

at higher risk for dementia. What the test cannot measure is when someone might develop a life-altering disease — or whether they will at all.