That loss of brain volume is a bad thing, resulting from the loss of necessary cells, is a concept central to the research and clinical fields. It occurs in the late stages of Alzheimer’s disease as cells die and cognitive function is lost. So it is interesting to see this view challenged in the context of the recently approved amyloid-clearing immunotherapies. Is brain volume loss following treatment a function of mechanisms other than loss of cells? Is it actually a beneficial outcome? I can see it requiring a great deal more time, funding, and data to convince the broader field that this is the case.
Researchers analysed data from a dozen different trials of amyloid-targeting immunotherapy. While brain shrinkage is usually an undesirable outcome, the team found that the excess volume loss was consistent across studies and correlated with how effective the therapy was in removing amyloid and was not associated with harm. As a result, the researchers believe that the removal of amyloid plaques, which are abundant in Alzheimer’s patients, could account for the observed brain volume changes. And, as such, the volume loss should not be a cause for concern.
To describe this phenomenon, the research team coined a new phrase: “amyloid-removal-related pseudo-atrophy” or ARPA. “Amyloid-targeting monoclonal antibodies represent a significant therapeutic breakthrough. One area of controversy has been the effect of these agents on brain volumes. Brain volume loss is a characteristic feature of Alzheimer’s disease, caused by progressive loss of neurons. 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 plaque. We are calling for better reporting of these changes in clinical trials.”
