FDG PET (and MRI) for Monitoring Immunotherapy in Alzheimer Disease

Passive immunotherapy for Alzheimer disease has been tried for over 10 years without success. However, in 2021 and most recently in January 2023, the US Food and Drug Administration granted accelerated approval of 2 antibodies for this purpose, aducanumab and lecanemab. In both cases, the approval was based on a presumed therapy-related removal of amyloid deposits from the brain and, in the case of lecanemab, also some delay in cognitive decline. We question the validity of the evidence for the removal of amyloid in particular as assessed by amyloid PET imaging, believing that what is observed is more likely a large nonspecific amyloid PET signal in the white matter that diminishes during immunotherapy—in line with dose-dependent increases in amyloid-related imaging abnormalities and increased loss of cerebral volume in treated compared with placebo patients. To investigate this further, we recommend repeat FDG PET and MRI in all future immunotherapy trials.