Tackling Alzheimer’s disease might be even harder than assumed. A report out today casts serious doubt on the latest drugs approved to treat the fatal neurodegenerative condition.
Researchers examined the clinical trial data surrounding anti-amyloid medications for Alzheimer’s. While the drugs were effective at clearing away amyloid beta from the brain, they had next to little benefit on people’s cognition and memory, the authors found. What’s more, the medications can cause significant complications like bleeding in the brain.
“Future research on disease‐modifying treatments for Alzheimer’s disease should focus on other treatments,” they concluded in their paper, published Thursday in the Cochrane Database of Systematic Reviews.
Not clinically meaningful
The Cochrane Library is a British-based group that regularly publishes comprehensive reviews. It specifically asks scientists, clinicians, and even patients themselves to analyze the clinical trial literature relevant to important public health topics, including Alzheimer’s disease.
The brains of people with Alzheimer’s become cluttered with the misfolded forms of two proteins, amyloid beta and tau. Some research has suggested that amyloid beta in particular drives the brain’s destruction in Alzheimer’s. And that’s led scientists to develop antibody-based drugs that try to eliminate amyloid from the brain, hoping to slow or even reverse Alzheimer’s symptoms.
In this latest review, researchers looked at 17 studies of anti-amyloid drugs that collectively included over 20,000 participants. These studies involved seven different drugs, three of which were approved in the U.S. and other countries to treat Alzheimer’s.
All told, the researchers found little to be excited about. Though these medications do reliably clear amyloid from the brain, this removal seemingly doesn’t translate to practical benefits. Compared to placebo, the drugs’ effect on people’s cognition or dementia severity was overall “trivial” over a 18-month period, the authors reported. Similarly, any effect on people’s functional ability was “small at best.”
At the same time, these drugs are known to cause something known as amyloid-related imaging abnormalities, or ARIAs, which are markers of swelling or bleeding of the brain. Though ARIAs can be a serious issue, the review did not find evidence that anti-amyloid drugs increase the risk of death compared to placebo. Still, the verdict in general is plenty gloomy.
“Unfortunately, the evidence suggests that these drugs make no meaningful difference to patients,” said lead author Francesco Nonino, a neurologist and epidemiologist at the IRCCS Institute of Neurological Sciences of Bologna, Italy, in a statement from the Cochrane Library.
What does this mean for Alzheimer’s research?
This isn’t the first time that scientists have questioned the usefulness of anti-amyloid drugs for Alzheimer’s, including drugs that had passed late stage clinical trials and were granted regulatory approval. And some of these drugs approved in the U.S. have since been pulled from the market or later failed to win approval in other countries.
The findings highlight a known issue in medicine: Just because a drug shows statistically significant results in a trial, that doesn’t necessarily mean it will significantly change patients’ lives for the better.
It is still possible these drugs could have a meaningful place in Alzheimer’s treatment. Some research has suggested that they might be able to substantially slow down progression in people who are genetically destined to develop early-onset Alzheimer’s, for instance. Other scientists are working on ways to boost the potency of these and other medications used in the brain.
And at least some Alzheimer’s organizations aren’t quite so pessimistic about amyloid-based therapies, arguing that they could someday be used with other interventions.
“Alzheimer’s disease is highly complex and a combination of treatments will likely be needed to target a range of processes involved in its development. Anti-amyloid drugs are just one treatment avenue and not a silver bullet,” said Richard Oakley, associate director of research and innovation at the Alzheimer’s Society, in a statement released by the group.
Finding a reliable treatment for Alzheimer’s will not be easy. Hopefully, though, it is still within our reach.
