Department of Psychiatry and Neuropsychology, Maastricht University, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht, The Netherlands.
Neurobiol Aging. 2012 Oct;33(10):2272-81. doi: 10.1016/j.neurobiolaging.2011.12.017. Epub 2012 Jan 20.
Our aim was to identify the best diagnostic test sequence for predicting Alzheimer's disease (AD)-type dementia in subjects with mild cognitive impairment (MCI) using cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI) biomarkers. We selected 153 subjects with mild cognitive impairment from a multicenter memory clinic-based cohort. We tested the CSF beta amyloid (Aβ)1-42/tau ratio using enzyme-linked immunosorbent assay (ELISA) and hippocampal volumes (HCVs) using the atlas-based learning embeddings for atlas propagation (LEAP) method. Outcome measure was progression to AD-type dementia in 2 years. At follow-up, 48 (31%) subjects converted to AD-type dementia. In multivariable analyses, CSF Aβ1-42/tau and HCV predicted AD-type dementia regardless of apolipoprotein E (APOE) genotype and cognitive scores. Test sequence analyses showed that CSF Aβ1-42/tau increased predictive accuracy in subjects with normal HCV (p < 0.001) and abnormal HCV (p = 0.025). HCV increased predictive accuracy only in subjects with normal CSF Aβ1-42/tau (p = 0.014). Slope analyses for annual cognitive decline yielded similar results. For selection of subjects for a prodromal AD trial, the best balance between sample size and number of subjects needed to screen was obtained with CSF markers. These results provide further support for the use of CSF and magnetic resonance imaging biomarkers to identify prodromal AD.
我们的目的是使用脑脊液 (CSF) 和磁共振成像 (MRI) 生物标志物来确定预测轻度认知障碍 (MCI) 患者发生阿尔茨海默病 (AD) 型痴呆的最佳诊断测试序列。我们从一个基于多中心记忆诊所的队列中选择了 153 名轻度认知障碍患者。我们使用酶联免疫吸附测定 (ELISA) 测试了 CSF 中β淀粉样蛋白 (Aβ)1-42/tau 比值，使用基于图谱的学习嵌入图谱传播 (LEAP) 方法测试了海马体积 (HCV)。结局指标为 2 年内进展为 AD 型痴呆。随访时，48 名 (31%)患者转化为 AD 型痴呆。在多变量分析中，CSF Aβ1-42/tau 和 HCV 预测 AD 型痴呆，与载脂蛋白 E (APOE) 基因型和认知评分无关。测试序列分析表明，CSF Aβ1-42/tau 在 HCV 正常的患者中提高了预测准确性（p<0.001），在 HCV 异常的患者中提高了预测准确性（p=0.025）。HCV 仅在 CSF Aβ1-42/tau 正常的患者中提高了预测准确性（p=0.014）。年度认知衰退斜率分析得出了类似的结果。对于选择进行前驱 AD 试验的患者，CSF 标志物可获得最佳的样本量和需要筛查的患者数量之间的平衡。这些结果为使用 CSF 和磁共振成像生物标志物来识别前驱 AD 提供了进一步的支持。
