Silbert L C, Quinn J F, Moore M M, Corbridge E, Ball M J, Murdoch G, Sexton G, Kaye J A
Aging and Alzheimer's Disease Center, Department of Neurology, Oregon Health and Science University, Portland 97201, USA.
Neurology. 2003 Aug 26;61(4):487-92. doi: 10.1212/01.wnl.0000079053.77227.14.
To assess whether changes in antemortem MRI brain volume measurements are valid predictors of subsequent Alzheimer disease (AD) pathology.
Thirty-nine subjects, 15 nondemented and 24 with cognitive impairment, were followed until death. Regional postmortem measures of senile plaque (SP) and neurofibrillary tangle (NFT) severity were examined in relationship to cross-sectional and longitudinal volumetric measurements obtained from antemortem MRI.
Total brain volume change over time was related to the accumulation of cortical NFT. The rate of ventricular CSF volume increase was related to both cortical NFT and SP. The last hippocampal volume prior to death was related to hippocampal NFT burden; the rate of hippocampal volume atrophy was not related to hippocampal NFT pathology. These significant relationships continue to exist when all nondemented subjects are excluded from analysis. In subjects with cognitive impairment, the best predictor of cortical NFT and SP is the rate of ventricular volume increase. Excluding subjects with long duration between MRI and death did not appreciably alter results.
MRI volumes measured over time are valid biomarkers of pathologic progression of AD across a range of antemortem clinical states. The rate of ventricular volume enlargement can be used to monitor disease progression or response to treatment in future clinical trials that are targeted at NFT and SP pathology.
评估生前MRI脑容量测量的变化是否是后续阿尔茨海默病（AD）病理的有效预测指标。
对39名受试者进行随访直至死亡，其中15名无痴呆，24名有认知障碍。将死后老年斑（SP）和神经原纤维缠结（NFT）严重程度的区域测量结果与生前MRI获得的横断面和纵向体积测量结果进行关联研究。
随着时间推移，全脑体积变化与皮质NFT的积累有关。脑室脑脊液体积增加率与皮质NFT和SP均有关。死亡前最后一次海马体积与海马NFT负担有关；海马体积萎缩率与海马NFT病理无关。当从分析中排除所有无痴呆受试者时，这些显著关系仍然存在。在有认知障碍的受试者中，皮质NFT和SP的最佳预测指标是脑室体积增加率。排除MRI检查与死亡之间间隔时间长的受试者对结果没有明显影响。
随时间测量的MRI体积是AD在一系列生前临床状态下病理进展的有效生物标志物。脑室体积增大率可用于在未来针对NFT和SP病理的临床试验中监测疾病进展或治疗反应。
