There is evidence to suggest that anti-amyloid therapies used to treat Alzheimer’s disease cause accelerated brain volume loss.
In some cases, certain classes of anti-amyloid beta (Aβ) drugs resulted in individuals’ brain volume decreasing more rapidly while using the drug than they would have if they had not received treatment at all.
These and other findings were published on March 27 in Neurology.
“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,” corresponding author of the new paper Scott Ayton, with the Florey Institute of Neuroscience and Mental Health in Melbourne, Australia, and co-authors explained.
The meta-analysis included 31 studies that assessed two different types of anti-amyloid drugs: secretase inhibitors and monoclonal antibodies (including aducanumab and lecanemab). Trial participants from these studies were eligible for inclusion only if anti-Aβ drugs had positively changed at least one biomarker of pathological amyloid beta and if detailed MRI data were available to assess volumetric changes in at least one region of the brain.
Experts found that accelerated brain atrophy varied based on drug class, with secretase inhibitors having a greater impact on brain volume loss than monoclonal antibodies. This was most prevalent within the hippocampus and whole brain.
In contrast, use of monoclonal antibodies resulted in an accelerated increase in ventricular enlargement. This finding was amplified when monoclonal antibodies caused amyloid-related imaging abnormalities (ARIA), with increased ARIA frequency having a “striking” correlation with ventricular enlargement.
As both ventricular enlargement and loss of brain volume are known to be associated with the progression of Alzheimer’s, the researchers’ findings brought additional questions to the surface regarding treatment of the neurological disease. For example, does the presence of ARIA in some patients indicate that they are more susceptible to accelerated neurodegeneration?
In an accompanying editorial, Frederik Barkhof, MD, PhD, of Amsterdam University Medical Center in the Netherlands, and David Knopman, MD, of the Mayo Clinic in Rochester, Minnesota, suggested answering this question and others requires further, long-term observation to fully understand the impact of AD treatments.
“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,” Barkhof and Knopman noted.
However, for this meta-analysis, the team was limited due to not having access to patient-level data from the trials included in their research. Experts involved in the research suggested that clinical trials testing AD treatments need “urgent” reevaluation with more emphasis placed on brain volume and ARIA.
The study abstract is available here, and the editorial here (paywall).
In addition to her background in journalism, Hannah also has patient-facing experience in clinical settings, having spent more than 12 years working as a registered rad tech. She joined Innovate Healthcare in 2021 and has since put her unique expertise to use in her editorial role with Health Imaging.