MRI Scans Highlight the Risks of Anti-Amyloid Drugs for Brain Volume Loss

Anti-amyloid treatments used to treat Alzheimer’s disease have been shown to accelerate brain volume loss.

While taking certain classes of anti-amyloid beta (A) medications, some people’s brain volume decreased more rapidly while using the drug than they would have if if they had not received any treatment at all.

On March 27, these and other findings were published in Neurology.

According to Scott Ayton, co-author of the new paper and corresponding author of the Florey Institute of Neuroscience and Mental Health in Melbourne, Australia, “These findings reveal the potential for anti-Aβ therapies to compromise long-term brain health by accelerating brain atrophy, and provide new insight into the adverse impact of ARIA.”

There were 31 studies included in the meta-analysis that looked at two different types of anti-amyloid drugs: monoclonal antibodies and secretase inhibitors (like aducanumab and lecanemab). If anti-Aβ drugs had a positive effect on at least one biomarker of pathological amyloid beta and if comprehensive MRI data were available to evaluate volumetric changes in at least one brain region, trial participants from these studies were eligible for inclusion.

Experts discovered that secretase inhibitors had a greater effect on brain volume loss than monoclonal antibodies did on accelerated brain atrophy depending on drug class. This was most common inside the hippocampus and the entire brain.

Monoclonal antibodies, on the other hand, caused ventricular enlargement to grow more quickly. Amyloid-related imaging abnormalities (ARIA), which were caused by monoclonal antibodies and had a “striking” correlation with ventricular enlargement, amplified this finding.

The findings of the researchers raised additional concerns regarding Alzheimer’s treatment because ventricular enlargement and brain volume loss are known to be linked to the disease’s progression. For example, does the presence of ARIA in some patients suggest that they are more likely to experience rapid neurodegeneration?

Frederik Barkhof, MD, Ph.D., of Amsterdam University Medical Center in the Netherlands, and David Knopman, MD, of the Mayo Clinic in Rochester, Minnesota, suggested in an accompanying editorial that in order to fully comprehend the effects of AD treatments, additional long-term observation is required to answer this question and others.

According to Barkhof and Knopman, “longer periods of observation will be needed to know whether the brain volume losses continue at an accelerated rate, or if they attenuate or disappear.”

However, the lack of patient-level data from the trials included in their research limited the team’s options for this meta-analysis. An “urgent” reevaluation of clinical trials testing AD treatments with a greater emphasis on brain volume and ARIA was suggested by researchers.