Devanand D P, Pradhaban G, Liu X, Khandji A, De Santi S, Segal S, Rusinek H, Pelton G H, Honig L S, Mayeux R, Stern Y, Tabert M H, de Leon M J
Department of Biological Psychiatry, New York State Psychiatric Institute, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Neurology. 2007 Mar 13;68(11):828-36. doi: 10.1212/01.wnl.0000256697.20968.d7.
To evaluate the utility of MRI hippocampal and entorhinal cortex atrophy in predicting conversion from mild cognitive impairment (MCI) to Alzheimer disease (AD).
Baseline brain MRI was performed in 139 patients with MCI, broadly defined, and 63 healthy controls followed for an average of 5 years (range 1 to 9 years).
Hippocampal and entorhinal cortex volumes were each largest in controls, intermediate in MCI nonconverters, and smallest in MCI converters to AD (37 of 139 patients converted to AD). In separate Cox proportional hazards models, covarying for intracranial volume, smaller hippocampal volume (risk ratio [RR] 3.62, 95% CI 1.93 to 6.80, p < 0.0001), and entorhinal cortex volume (RR 2.43, 95% CI 1.56 to 3.79, p < 0.0001) each predicted time to conversion to AD. Similar results were obtained for hippocampal and entorhinal cortex volume in patients with MCI with Mini-Mental State Examination (MMSE) scores > or = 27 out of 30 (21% converted to AD) and in the subset of patients with amnestic MCI (35% converted to AD). In the total patient sample, when both hippocampal and entorhinal volume were entered into an age-stratified Cox model with sex, MMSE, education, and intracranial volume, smaller hippocampal volume (RR 2.21, 95% CI 1.14 to 4.29, p < 0.02) and entorhinal cortex volume (RR 2.48, 95% CI 1.54 to 3.97, p < 0.0002) predicted time to conversion to AD. Similar results were obtained in a Cox model that also included Selective Reminding Test (SRT) delayed recall and Wechsler Adult Intelligence Scale-Revised (WAIS-R) Digit Symbol as predictors. Based on logistic regression models in the 3-year follow-up sample, for a fixed specificity of 80%, the sensitivities for MCI conversion to AD were as follows: age 43.3%, MMSE 43.3%, age + MMSE 63.7%, age + MMSE + SRT delayed recall + WAIS-R Digit Symbol 80.6% (79.6% correctly classified), hippocampus + entorhinal cortex 66.7%, age + MMSE + hippocampus + entorhinal cortex 76.7% (85% correctly classified), age + MMSE + SRT delayed recall + WAIS-R Digit Symbol + hippocampus + entorhinal cortex 83.3% (86.8% correctly classified).
Smaller hippocampal and entorhinal cortex volumes each contribute to the prediction of conversion to Alzheimer disease. Age and cognitive variables also contribute to prediction, and the added value of hippocampal and entorhinal cortex volumes is small. Nonetheless, combining these MRI volumes with age and cognitive measures leads to high levels of predictive accuracy that may have potential clinical application.
评估磁共振成像（MRI）海马体及内嗅皮质萎缩在预测轻度认知障碍（MCI）向阿尔茨海默病（AD）转化中的作用。
对139例广义定义的MCI患者及63名健康对照者进行了基线脑MRI检查，并对其进行了平均5年（范围1至9年）的随访。
对照组的海马体和内嗅皮质体积最大，未转化为AD的MCI患者的体积居中，转化为AD的MCI患者（139例患者中有37例转化为AD）的体积最小。在单独的Cox比例风险模型中，校正颅内体积后，较小的海马体体积（风险比[RR] 3.62，95%置信区间1.93至6.80，p < 0.0001）和内嗅皮质体积（RR 2.43，95%置信区间1.56至3.79，p < 0.0001）均能预测向AD转化的时间。在简易精神状态检查表（MMSE）评分≥27分（满分30分）的MCI患者（21%转化为AD）以及遗忘型MCI患者亚组（35%转化为AD）中，海马体和内嗅皮质体积也得到了类似结果。在全部患者样本中，将海马体和内嗅皮质体积纳入一个按年龄分层并包含性别、MMSE、受教育程度及颅内体积的Cox模型时，较小的海马体体积（RR 2.21，95%置信区间1.14至4.29，p < 0.02）和内嗅皮质体积（RR 2.48，95%置信区间1.54至3.97，p < 0.0002）可预测向AD转化的时间。在一个还纳入了选择性提醒测试（SRT）延迟回忆及韦氏成人智力量表修订版（WAIS-R）数字符号作为预测指标的Cox模型中也得到了类似结果。基于3年随访样本的逻辑回归模型，对于固定为80%的特异性，MCI转化为AD的敏感度如下：年龄43.3%，MMSE 43.3%，年龄+MMSE 63.7%，年龄+MMSE+SRT延迟回忆+WAIS-R数字符号80.6%（正确分类率79.6%），海马体+内嗅皮质66.7%，年龄+MMSE+海马体+内嗅皮质76.7%（正确分类率85%），年龄+MMSE+SRT延迟回忆+WAIS-R数字符号+海马体+内嗅皮质83.3%（正确分类率86.8%）。
较小的海马体和内嗅皮质体积均有助于预测向阿尔茨海默病的转化。年龄和认知变量也有助于预测，且海马体和内嗅皮质体积的附加值较小。尽管如此，将这些MRI体积测量值与年龄及认知指标相结合可实现较高水平的预测准确性，这可能具有潜在的临床应用价值。
