Anti‐amyloid immunotherapy and brain volume trajectories in early‐onset versus late‐onset Alzheimer's disease

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Abstract INTRODUCTION Accelerated brain volume loss has been observed following trials of anti‐amyloid beta immunotherapy (AAT); however, there is limited understanding of this paradoxical phenomenon in early‐onset Alzheimer's disease (EOAD) versus late‐onset Alzheimer's disease (LOAD). METHODS We retrospectively analyzed brain volume changes over a 1‐year period following initiation of AAT. Annualized rates of brain volume alteration were calculated, and linear mixed‐effects models were performed to assess brain volume trajectories in EOAD versus LOAD. RESULTS One hundred fourteen participants (35 with EOAD; 79 with LOAD; mean baseline MMSE: 27) were analyzed. Ventricular expansion, measuring ∼15%/year, and whole‐brain atrophy occurred in both groups. LOAD showed ∼1.7× greater hippocampal atrophy compared with EOAD, independent of baseline cerebral amyloid burden, though global cortical amyloid burden predicted whole‐brain and hippocampal atrophy ( p < 0.001). DISCUSSION Brain atrophy with prominent ventricular expansion occurs in early‐stage EOAD and LOAD following AAT. Additional studies are needed to elucidate the mechanisms and implications of this post‐immunotherapy effect.

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