A groundbreaking new study shows that anti-amyloid medications have no meaningful benefit for patients.
Drugs designed to remove amyloid plaques from the brain have no clinical benefit for people with early Alzheimer’s disease, according to researchers.
In what one expert described as the best independent test of whether reducing plaque improves memory, thinking, daily function and independence, the team from the IRCCS Istitutodelle Scienze Neurologiche di Bologna, Italy, has cast serious doubt.
“After decades without a meaningful breakthrough, Australia has recently approved lecanemab and donanemab, anti-amyloid drugs hailed as the first medicines that might finally slow Alzheimer’s disease rather than simply manage symptoms,” Professor Bryce Vissel from the School of Clinical Medicine at UNSW told media.
“For families watching a loved one lose memory, judgement and independence, the promise has carried enormous hope.
“But a major Cochrane review, pooling 17 trials involving 20,342 people, delivers a far more sobering verdict: overall, it says, these drugs do not provide a benefit that most people in the early stages of Alzheimer’s would find meaningful, while brain swelling occurred in about 119 per every 1000 on treatment.”
The studies, conducted between 2014 and 2024, tested several anti-amyloid monoclonal antibodies against placebo over periods of 18 to more than 24 months.
After 18 months of treatment, cognitive function and dementia severity showed little to no difference compared with placebo (SMD −0.11 and −0.12, respectively), while functional ability remained largely unchanged (SMD 0.09).
While some measures of more complex daily activities suggested small improvements (SMD up to 0.23), these effects were considered clinically trivial, falling well below thresholds regarded as meaningful for patients.
Importantly, even when amyloid plaques were successfully cleared from the brain – as seen in imaging studies – this did not translate into noticeable improvements in memory, thinking or daily functioning.
“[The review] is the best independent test of whether a dramatic effect on amyloid PET scans translates into a meaningful benefit for patients,” said Professor Vissel.
“Its answer is sobering: even when plaques are successfully cleared, the hoped-for improvements in memory, thinking, daily function and independence do not meaningfully follow. In plain English, these drugs clear plaques far more convincingly than they preserve memory, thinking and independence.”
“This Cochrane review forces a blunt question: if these drugs remove the very plaques long thought to drive Alzheimer’s, why are patients not getting a meaningful improvement in memory, thinking, daily function or independence?”
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With Alzheimer’s disease cases rising globally, from 26.6 million in 2006 to a projected 106 million by 2050, the findings highlight the urgent need for new therapeutic approaches beyond amyloid targeting.
“Amyloid may still play a role, and future therapies aimed at it may yet prove useful, but the field now needs a broader, more individualised medicine approach with a sharp focus on preserving cognition, daily function and independence,” said Professor Vissel.
The review found that the treatments were also consistently associated with higher rates of amyloid-related imaging abnormalities, particularly brain swelling (ARIA-E). The researchers found an additional 107 cases per 1000 patients experienced ARIA-E compared with placebo.
There was also evidence of increased microbleeds in the brain, although results varied across studies. Despite this, rates of serious adverse events and mortality were not significantly increased in those treated (six more per 1000 and two more per 1000, respectively).
Mean participant age ranged from 69.5 to 73.9 years, and the proportion of female participants ranged from 50% to 64.5%. The mean duration of cognitive impairment ranged from 16.8 to 51.6 months. Race and ethnicity reporting was limited but no study had less than 75% White participants. No studies reported socioeconomic status.
Of the 17 RCTs, seven included only participants with mild dementia, one included only participants with mild cognitive impairment (MCI) and nine included a mixed population. All used parallel-group designs, with no cluster or crossover trials included, comparing anti-amyloid monoclonal antibodies to placebo. All were funded by pharmaceutical companies manufacturing anti-amyloid drugs.
They were conducted across many international centres, including North America, Europe, Asia, Australia and South America. Medications used were aducanumab (three studies), bapineuzumab (four), crenezumab (two), donanemab (one), gantenerumab (four), lecanemab (one) and solanezumab (two).
