Missing tissue, missing data: Resolving brain volume loss caused by anti-amyloid therapies

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Source: PLOS Medicine

Original: https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1004880...

Published: 2026-01-20T14:00:00Z

Anti-amyloid drugs slightly slow the progression of Alzheimer's disease, but cause a paradoxical acceleration of brain volume changes.[1][2] A meta-analysis of 31 clinical trials at the highest doses showed accelerated volume changes in the hippocampus, lateral ventricles, and whole brain.[2][3] Secretase inhibitors accelerated hippocampal atrophy by 37.1 µl (19.6% more than placebo) and whole brain atrophy by 3.3 ml (21.8% more than placebo).[2] ARIA-inducing monoclonal antibodies accelerated ventricular enlargement by 2.1 mL (38.7% more than placebo), with a correlation between ventricular volume and ARIA frequency (r=0.86; p=6.22×10⁻⁷).[2][3] In patients with mild cognitive impairment, treatment with antiamyloid drugs resulted in brain volume regressions typical of Alzheimer's dementia approximately 8 months earlier.[2][3] The study calls for transparent disclosure of data from clinical trials.[1]