Brain Shrinkage in Anti–β-Amyloid Alzheimer Trials

One of the puzzling observations from anti–amyloid-β therapeutic trials for Alzheimer disease (AD) has been that treated arms fail to show preservation of brain volume. In this issue of Neurology ®, Alves et al.1 presented a meta-analysis of anti–amyloid-β therapies and show that the agents do not slow the rate of brain volume loss. Depending on the class of drug, these new agents can even accelerate loss of whole-brain and hippocampal volume and increase ventricular volume. This association has been seen with some of the beta-secretase inhibitors and with several of the antiamyloid monoclonal antibodies.