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.
Clinical Neurosciences, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
Lancet Neurol. 2024 Oct;23(10):1025-1034. doi: 10.1016/S1474-4422(24)00335-1.
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.
MRI 上进行性脑容量损失是阿尔茨海默病的标志，并已被广泛用作临床试验的结果衡量标准，预测疾病修饰治疗将减缓损失。然而，在抗淀粉样蛋白免疫疗法的试验中，接受治疗的参与者出现了脑容量过度损失。对这一观察结果的解释范围从减少淀粉样蛋白β斑块负担和相关炎症变化，到治疗引起的毒性。这种过量的体积变化仅发生在那些能降低淀粉样蛋白β水平的免疫疗法中；与斑块清除相兼容；并且迄今为止的证据表明，与有害影响无关。基于目前的证据，我们建议将这些变化描述为与淀粉样蛋白清除相关的假性萎缩。更好地了解这些变化的原因和后果对于做出明智的治疗决策非常重要。需要对试验数据进行患者水平的分析，以及进行纵向随访和神经影像学数据，以确定这些体积变化的长期轨迹及其临床相关性。对接受治疗的患者的脑组织进行尸检检查，并评估与生前神经影像学发现的潜在相关性，是关键的优先事项。
