Department of Neurology, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea.
Department of Neurology, Inje University College of Medicine, Haeundae Paik Hospital, Busan, Korea.
J Alzheimers Dis. 2018;66(2):681-691. doi: 10.3233/JAD-180048.
Most clinical trials focus on amyloid-β positive (Aβ+) amnestic mild cognitive impairment (aMCI), but screening failures are high because only a half of patients with aMCI are positive on Aβ PET. Therefore, it becomes necessary for clinicians to predict which patients will have Aβ biomarker.
We aimed to compare clinical factors, neuropsychological (NP) profiles, and apolipoprotein E (APOE) genotype between Aβ+ aMCI and Aβ-aMCI and to develop a clinically useful prediction model of Aβ positivity on PET (PET-Aβ+) in aMCI using a nomogram.
We recruited 523 aMCI patients who underwent Aβ PET imaging in a nation-wide multicenter cohort. The results of NP measures were divided into following subgroups: 1) Stage (Early and Late-stage), 2) Modality (Visual, Verbal, and Both), 3) Recognition failure, and 4) Multiplicity (Single and Multiple). A nomogram for PET-Aβ+ in aMCI patients was constructed using a logistic regression model.
PET-Aβ+ had significant associations with NP profiles for several items, including high Clinical Dementia Rating Scale Sum of Boxes score (OR 1.47, p = 0.013) and impaired memory modality (impaired both visual and verbal memories compared with visual only, OR 3.25, p = 0.001). Also, presence of APOEɛ4 (OR 4.14, p < 0.001) was associated with PET-Aβ+. These predictors were applied to develop the nomogram, which showed good prediction performance (C-statistics = 0.79). Its prediction performances were 0.77/0.74 in internal/external validation.
The nomogram consisting of NP profiles, especially memory domain, and APOEɛ4 genotype may provide a useful predictive model of PET-Aβ+ in patients with aMCI.
大多数临床试验都集中在淀粉样蛋白-β 阳性（Aβ+）遗忘型轻度认知障碍（aMCI）上，但筛查失败率很高，因为只有一半的 aMCI 患者 Aβ PET 阳性。因此，临床医生有必要预测哪些患者会有 Aβ 生物标志物。
我们旨在比较 Aβ+ aMCI 和 Aβ-aMCI 之间的临床因素、神经心理学（NP）特征和载脂蛋白 E（APOE）基因型，并使用列线图为 aMCI 患者的 Aβ 阳性 PET（PET-Aβ+）建立一个具有临床应用价值的预测模型。
我们招募了 523 名在全国多中心队列中接受 Aβ PET 成像的 aMCI 患者。NP 测量结果分为以下亚组：1）阶段（早期和晚期），2）模态（视觉、言语和两者），3）识别失败，和 4）多发性（单发性和多发性）。使用逻辑回归模型构建了用于 aMCI 患者 PET-Aβ+的列线图。
PET-Aβ+与 NP 特征的几个项目显著相关，包括较高的临床痴呆评定量表总分（OR 1.47，p = 0.013）和记忆障碍模式（与仅视觉相比，视觉和言语记忆均受损，OR 3.25，p = 0.001）。此外，APOEɛ4 的存在（OR 4.14，p < 0.001）与 PET-Aβ+相关。这些预测因子被应用于开发列线图，该列线图显示了良好的预测性能（C 统计量= 0.79）。其内部/外部验证的预测性能分别为 0.77/0.74。
由 NP 特征（尤其是记忆域）和 APOEɛ4 基因型组成的列线图可能为 aMCI 患者的 PET-Aβ+提供有用的预测模型。
