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

Abstract

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.

Use of lecanemab for the treatment of Alzheimer's disease: A systematic review

“…The removal of amyloid plaques observed on PET scans of Alzheimer's patients may be explained by the damage. To evaluate the deleterious consequences, FDG‐PET imaging should be used in further research both before and after antibody therapy (Høilund‐Carlsen et al., 2023 ). Additionally, new research indicates that antibody therapies significantly reduce the amount of brain tissue as determined by MRI (Høilund‐Carlsen et al., 2023 ).…”

Lecanemab (Leqembi) is not the right drug for patients with Alzheimer’s disease

“…Indeed, as argued by Høilund-Carlsen et al, the specificity and sensitivity of PET in measuring Aβ amyloid in the brain have not been proven. 25 The idea to use anti-Aβ antibodies in AD immunotherapy is based on the amyloid hypothesis, 26,27 which proposes that Aβ peptide amyloid formations in the brain cause AD. Thus, the hypothesis predicts that the removal of brain amyloid provides a treatment for AD patients, and preventing brain amyloid formation inhibits the development of AD.…”