Alzheimer's & dementia (Amsterdam, Netherlands) · 2026
Anti-amyloid immunotherapy and brain volume trajectories in early-onset versus late-onset Alzheimer's disease.
СтатьяНазвание и аннотация: Перевод в очереди
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Mehta Rashi I, Jaisa-Aad Methasit, Teixeira Camila Vieira Ligo, Worhunsky Patrick D, Malone Joseph E, Ward Melanie, Keith Cierra M, Phelps Holly E, Sharif Khalid, Pockl Stephanie, Rajabalee Nafiisah, Marano Gary D, Bojarski Lauren, Smith Samantha, Massey Kayla M, Hatfield Marcus, D'Haese Pierre-François, Rezai Ali R, Haut Marc W
Аннотация
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.
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.