Rashi I Mehta, Methasit Jaisa-Aad, Camila Vieira Ligo Teixeira, Patrick D Worhunsky, Joseph E Malone, Melanie Ward, Cierra M Keith, Holly E Phelps, Khalid Sharif, Stephanie Pockl, Nafiisah Rajabalee, Gary D Marano, Lauren Bojarski, Samantha Smith, Kayla M Massey, Marcus Hatfield, Pierre-François D'Haese, Ali R Rezai, Marc W Haut
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).
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.