Drugs that have been marketed as a gamechanger for Alzheimer’s are, according to an extensive review, making no noticeable difference for patients.
The analysis—based on clinical trials in people with mild cognitive impairment or mild dementia—looked at how anti-amyloid treatments affect cognition and dementia severity over 18 months. Its conclusion is blunt: the effects were “trivial,” with improvements in functional ability “small at best.” In the background is the familiar biology story—amyloid plaques, clumps of amyloid protein, are a hallmark of Alzheimer’s alongside tau tangles in neurons. The newer wave of medicines is built on that idea: clear amyloid, slow decline.
But the review also lands hard on how the evidence has been assembled. Misryoum newsroom reported that the Cochrane review used gold standard methods to assess data from published trials, even as some researchers and charities criticized it for mixing older, failed drugs with newer, more effective medicines. That tension matters because the “average” benefit can shrink when effective and ineffective treatments are pooled together—something Misryoum analysis indicates the review itself can’t neatly undo.
Misryoum newsroom reported that Charles Marshall, professor of clinical neurology at Queen Mary, University of London, said the logic of pooling is straightforward: if you combine results from effective and ineffective treatments, you end up with a small or absent average treatment effect. Meanwhile, Misryoum newsroom reported that regulators in multiple countries approved lecanemab, made by Eisai, and donanemab, made by Eli Lilly. Yet many places stopped short of funding them through public health services. In the UK, the National Institute for Health and Care Excellence (Nice) said that even though the drugs slowed the disease by four to six months, the cost to the NHS wasn’t justified. Nice is revisiting that decision after an appeal by the manufacturers.
The numbers in the review are substantial. Misryoum newsroom reported that the Cochrane analysis examined 17 clinical trials, typically lasting 18 months, involving more than 20,000 people. Seven anti-amyloid drugs were assessed, and all focused on people at the earlier stages—mild cognitive impairment or mild dementia. Edo Richard, co-author of the review and professor of neurology at Radboud University medical centre in the Netherlands, said the analysis found “no clinically meaningful effect on cognitive decline or dementia severity.” He also argued that the drugs came with more harm than the placebo, with more swelling and bleeding in the brain.
Richard’s other point was practical and, frankly, relentless: even if trials show a small signal, Misryoum newsroom reported that patients and caregivers might not be able to feel it. The effect sizes are too small “for patients and caregivers to notice,” he said, and the treatment is “burdensome.” Patients must visit a clinic every two to four weeks for intravenous infusions, plus have regular MRI scans to check for brain swelling or bleeding. He defended pooling across different drugs because they all aimed to remove amyloid and were assessed in comparable ways.
Not everyone agrees the concern is only about math. Robert Howard, professor of old age psychiatry at UCL, said emerging trial data raises doubts about whether anti-amyloid drugs truly alter Alzheimer’s’ course. Misryoum newsroom reported his warning that it’s “not fair on patients to have expectations raised,” adding that even the best-performing drugs don’t do anything “clinically meaningful.” In a separate response, Misryoum newsroom reported that Dr Susan Kohlhaas at Alzheimer’s Research UK argued the review paints a whole drug class with the same brush. She said only two of the 17 studies included medicines now approved in the UK—lecanemab and donanemab—while the rest focused on drugs that were not pursued after failing to show meaningful benefit, shaping the review’s conclusions. Her bottom line was that anti-amyloid treatments shouldn’t be dismissed as “trivial,” especially given constraints in what the analysis can tell.
Somewhere between the courtroom language of “effect sizes” and the lived reality of clinic schedules, the message is getting sharpened: the field may need new strategies beyond amyloid alone. And after reading the review, it’s hard not to think about the sound of a hospital MRI room—steady, repetitive—when you consider how often patients must undergo checks, or maybe, that’s just what my brain does when it’s trying to stay calm while the science isn’t. What’s clear, at least, is that the review calls for researchers to explore new ways to treat Alzheimer’s, even if the debate over anti-amyloid’s value isn’t going to disappear.
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