Ridha Basil H, Barnes Josephine, Bartlett Jonathan W, Godbolt Alison, Pepple Tracey, Rossor Martin N, Fox Nick C
Dementia Research Centre, University College London, Institute of Neurology, London, UK.
Lancet Neurol. 2006 Oct;5(10):828-34. doi: 10.1016/S1474-4422(06)70550-6.
Serial MRI scanning of autosomal dominant mutation carriers for Alzheimer's disease provides an opportunity to track changes that could predate symptoms or clinical diagnosis of the disease. We used hierarchical modelling to assess how hippocampal and whole-brain volumes change as familial Alzheimer's disease progresses from the presymptomatic stage through to diagnosis.
Nine mutation carriers had serial clinical assessments and volumetric MRI scans (41 scans: range 3-8 per patient) at different clinical stages (presymptomatic, mild cognitive impairment, or clinical Alzheimer's disease). 25 healthy controls had serial scanning (54 scans: range 2-4 per patient) for comparison. We measured whole brain and total hippocampal volumes using semi-automated techniques, and adjusted for total intracranial volume. Hierarchical models were developed to estimate differences in volume and atrophy rate between mutation carriers and controls in relation to when the disease was clinically diagnosed.
Mutation carriers had significantly increased hippocampal and whole-brain atrophy rates compared with controls and these differences increased with time. Differences in hippocampal and whole-brain atrophy rates between controls and mutation carriers were evident 5.5 and 3.5 years, respectively, before diagnosis of Alzheimer's disease. At a cross-sectional level, differences in mean hippocampal volume between mutation carriers and controls became significant 3 years before clinical diagnosis, whereas differences in mean brain volumes became significant only 1 year before diagnosis.
Structural changes can be seen on MRI scans that predate the clinical onset of familial Alzheimer's disease. Longitudinal measures of atrophy rates can identify differences between mutation carriers and controls 2-3 years earlier than cross-sectional volumetric measures.
对常染色体显性突变携带者进行阿尔茨海默病的系列磁共振成像（MRI）扫描，为追踪疾病症状或临床诊断之前的变化提供了机会。我们采用分层模型评估随着家族性阿尔茨海默病从症状前阶段发展至诊断阶段，海马体和全脑体积如何变化。
9名突变携带者在不同临床阶段（症状前、轻度认知障碍或临床阿尔茨海默病）接受了系列临床评估和容积MRI扫描（41次扫描：每位患者3 - 8次）。25名健康对照者接受了系列扫描（54次扫描：每位患者2 - 4次）用于比较。我们使用半自动技术测量全脑和海马体总体积，并对总颅内体积进行了校正。开发分层模型以估计突变携带者与对照者在疾病临床诊断时的体积差异和萎缩率差异。
与对照者相比，突变携带者的海马体和全脑萎缩率显著增加，且这些差异随时间增加。在阿尔茨海默病诊断前5.5年和3.5年，对照者与突变携带者之间的海马体和全脑萎缩率差异分别明显。在横断面水平上，突变携带者与对照者之间的平均海马体体积差异在临床诊断前3年变得显著，而平均脑体积差异仅在诊断前1年变得显著。
在家族性阿尔茨海默病临床发病之前，MRI扫描就能发现结构变化。萎缩率的纵向测量比横断面容积测量能够提前2 - 3年识别突变携带者与对照者之间的差异。
