Belder, CRS;
Boche, D;
Nicoll, JAR;
Jaunmuktane, Z;
Zetterberg, H;
Schott, JM;
Barkhof, F;
(2024)
Brain volume change following anti-amyloid β immunotherapy for Alzheimer's disease: amyloid-removal-related pseudo-atrophy.
The Lancet Neurology
, 23
(10)
pp. 1025-1034.
10.1016/S1474-4422(24)00335-1.
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Abstract
Progressive 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.
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