• Christopher R S Belder, Delphine Boche, NicollJames A RJARClinical Neurosciences, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK., Zane Jaunmuktane, Henrik Zetterberg, Jonathan M Schott, Frederik Barkhof, and Nick C Fox.
• Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, UK; UK Dementia Research Institute at UCL, University College London, London, UK; Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia.
• Lancet Neurol. 2024 Oct 1; 23 (10): 102510341025-1034.

AbstractProgressive cerebral volume loss on MRI is a hallmark of Alzheimer's disease and has been widely used as an outcome measure in clinical trials, with the prediction that disease-modifying treatments would slow loss. However, in trials of anti-amyloid immunotherapy, the participants who received treatment had excess volume loss. Explanations for this observation range from reduction of amyloid β plaque burden and related inflammatory changes through to treatment-induced toxicity. The excess volume changes are characteristic of only those immunotherapies that achieve amyloid β lowering; are compatible with plaque removal; and evidence to date does not suggest an association with harmful effects. Based on the current evidence, we suggest that these changes can be described as amyloid-removal-related pseudo-atrophy. Better understanding of the causes and consequences of these changes is important to enable informed decisions about treatments. Patient-level analyses of data from the trials are urgently needed, along with longitudinal follow-up and neuroimaging data, to determine the long-term trajectory of these volume changes and their clinical correlates. Post-mortem examination of cerebral tissue from treated patients and evaluation of potential correlation with antemortem neuroimaging findings are key priorities.Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.

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