Brain shrinkage seen in patients taking Alzheimer’s wonder drugs may be a sign that the treatments are working rather than a harmful side effect, a study suggests.
The first drugs proven to slow the disease’s progression have been hailed as a major breakthrough in the battle against dementia.
But some scientists raised concerns that patients lost up to three teaspoons of brain volume in clinical trials.
One analysis published in the journal Neurology last year warned that the drugs may “compromise long-term brain health by accelerating brain atrophy”.
However, a new study led by experts at UCL suggests the brain shrinkage seen in trials may be caused by the removal of toxic amyloid plaques.
Looking at data from a dozen different trials, they found volume loss was only seen in patients taking drugs that successfully removed amyloid.
The amount of brain shrinkage correlated with how effective a drug was and did not appear to be linked with worse memory and thinking abilities, the researchers said.
As a result, they suggested the phenomenon was not cause for concern and should be called “amyloid-removal-related pseudo-atrophy”.
Senior author Professor Nick Fox, director of the UCL Dementia Research Centre, said: “Amyloid immunotherapy has consistently shown an increase in brain volume loss – leading to concerns in the media and medical literature that these drugs could be causing unrecognised toxicity to the brains of treated patients.
“However, based on the available data, we believe that this excess volume change is an anticipated consequence of the removal of pathologic amyloid plaques from the brain of patients with Alzheimer’s disease.”
The Neurology study said the amount of toxic protein cleared from the brain alone was too small to account for the volume losses.
However, the UCL team argued that plaques formed in patients’ brains “occupy a volume much greater than that due to the amyloid beta protein itself” as they also contain other components.
And they called for further research as the drugs become more widely available to determine whether brain shrinkage was an indicator of efficacy rather than a cause for concern.
David Thomas, head of policy and public affairs at Alzheimer’s Research UK, agreed that further investigation was needed to better understand how the treatments affect the brain.
He added: “While this review presents possible reasons for this loss of brain volume, more longer-term studies that track this change during and after treatment, alongside monitoring cognitive function and side effects, are needed.”
Lecanemab is the world’s first treatment proven to delay disease progression. Trials showed it could slow cognitive decline by around five months.
It was licensed for UK use after regulators carefully considered safety data but the hopes of thousands of people facing the heartache of dementia were dashed in August when the drug was rejected for NHS use.
Mr Thomas added: “Lecanemab and donanemab are the first drugs that can slow the decline of memory and thinking in people with early Alzheimer’s disease. They are very much the start of our journey, not the end.
“With people now receiving these therapies in health services across the world, it will be vital to collect as much data as possible around how these first-of-a-kind treatments work in the clinic.
“Alongside the information gathered in clinical trials, this will give us a greater understanding of how these new drugs work and needs to be a key consideration for the UK when thinking about how we enable access to new licensed medicines.”
The findings were published in the journal Lancet Neurology
