Anti-amyloid drugs for Alzheimers don't seem to work
By Olivia Henry, the Australian Science Media Centre
Certain drugs for Alzheimer’s disease may not be having any meaningful effect, according to international researchers who reviewed 17 past clinical trials involving over 20,000 participants.
The review focused specifically on drugs that target amyloid plaques – clumps of protein that build up in the brain and are often associated with Alzheimer’s disease.
Due to their association with Alzheimer’s disease and dementia, amyloid plaques have long been a focus of dementia research. But the current study calls this focus into question.
“These comments will spark intense debate,” Professor Amy Brodtmann from Monash University and the Florey Institute of Neuroscience and Mental Health, who was not involved in the study, told the AusSMC.
“The Alzheimer’s disease field still contains a solid majority of adherents to the amyloid hypothesis … however, there will be many clinicians who welcome this objective guidance for evidence-based care,” she added.
But it’s not just the lack of effectiveness that raises concerns – the review also found an increase in the risk of bleeding and swelling in the brain for people who take the drug.
And while there were no apparent symptoms of this swelling and bleeding for most patients, the authors say long-term effects of this remain uncertain.
Dr Bryce Vissel, a professor at the University of New South Wales called the results “sobering”.
“For families watching a loved one lose memory, judgment, and independence, the promise has carried enormous hope,” he said.
But when looking at the drugs’ effects on daily function and independence, “any slowing of decline was small at best and far from the kind of change patients and families would recognise as a breakthrough,”
“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?” he said.
But the results don’t necessarily prove amyloid has no role in Alzheimer’s, Dr Vissel added, they just show the current generation of anti-amyloid drugs is not necessarily delivering its original promise.
While the findings may be disheartening for many, they do not remove all hope from patients and families affected by Alzheimer’s and dementia.
Dr Nikki-Anne Wilson from UNSW and Neuroscience Research Australia (NeuRA) told the AusSMC the drugs were always limited to very specific cases, and the brain is complex, so any single treatment “is unlikely to offer the magic bullet we seek.”
These findings can help refocus our attention on other areas, she added, such as the 14 approaches to reduce the risk of dementia outlined in a Lancet Commission on Dementia prevention, intervention and care.
“For example, exercise may offer neuroprotective effects by reducing inflammation, building cognitive reserve, and reducing depression,” she said.
Professor Edo Richard, a senior author on the study from Radboud University Medical Centre in the Netherlands, said that while existing drugs offer some benefit for some patients, “there remains a high unmet need for more effective treatments.”
“I see Alzheimer’s patients in my clinic every week, and I wish I had an effective treatment to offer them,” he said.
Dr Vissel agreed, adding that this study might help guide a pathway forward.
“We have long argued that while amyloid has a role in the disease, it alone does not explain Alzheimer’s dementia,” he said.
“The way forward is to widen the lens: focus on the molecular and cellular biology of what is going wrong inside vulnerable brain cells and synapses, and develop genuinely individualised treatments.”
“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."
You can read the full AusSMC Expert Reaction here.
This article originally appeared in Science Deadline, a weekly newsletter from the AusSMC. You are free to republish this story, in full, with appropriate credit.
Contact: Olivia Henry
Phone: +61 8 7120 8666
Email: info@smc.org.au