Department of Psychiatry, The University of Texas Health Science Center, San Antonio, TX, USA.
Department of Medicine, The University of Texas Health Science Center, San Antonio, TX, USA.
J Alzheimers Dis. 2019;67(1):67-79. doi: 10.3233/JAD-171053.
Dementia can be empirically described by the latent dementia phenotype "δ" and its various composite "homologs". We have explored δ's blood-based protein biomarkers in the Texas Alzheimer's Research and Care Consortium (TARCC) study. However, it would be convenient to replicate those associations in the Alzheimer's Disease Neuroimaging Initiative (ADNI). To this end, we have engineered a δ homolog from observed cognitive performance measures common to both projects. Our findings were replicated in randomly selected 50% splits of TARCC data (Group 1, N = 1,747; Group 2, N = 1,755), and then independently in ADNI (N = 1,737). The new δ homolog, i.e., "dT2A" (d-TARCC to ADNI), fit the data of both studies well, and was strongly correlated with dementia severity, as rated by the Clinical Dementia Rating Scale "sum of boxes" (TARCC: r = 0.99, p < 0.001; ADNI: r = 0.96, p < 0.001). dT2A achieved an area under the receiver operating characteristic curve of 0.981 (0.976-0.985) for the discrimination of Alzheimer's disease from normal controls in TARCC, and 0.988 (0.983-0.993) in ADNI. dT2A is the 12th δ homolog published to date, and opens the door to independent replications across these and similar studies.
痴呆症可以通过潜在的痴呆表型“δ”及其各种组合“同源物”进行经验描述。我们已经在德克萨斯州阿尔茨海默病研究和护理联合会（TARCC）研究中探索了基于血液的 δ 蛋白生物标志物。然而，如果能在阿尔茨海默病神经影像学倡议（ADNI）中复制这些关联，那将是很方便的。为此，我们根据两个项目中共同的观察认知表现测量标准，设计了一个 δ 同源物。我们的发现分别在 TARCC 数据的随机选择的 50%分割（第 1 组，N=1747；第 2 组，N=1755）中得到了复制，然后在 ADNI 中独立得到了复制（N=1737）。新的 δ 同源物，即“dT2A”（从 TARCC 到 ADNI），很好地拟合了这两项研究的数据，并且与痴呆严重程度（由临床痴呆评定量表“总和评分”评定）强烈相关（TARCC：r=0.99，p<0.001；ADNI：r=0.96，p<0.001）。dT2A 在 TARCC 中用于区分阿尔茨海默病患者和正常对照者的诊断，其受试者工作特征曲线下面积为 0.981（0.976-0.985），在 ADNI 中的为 0.988（0.983-0.993）。dT2A 是迄今为止发表的第 12 个 δ 同源物，为在这些研究和类似研究中进行独立复制开辟了道路。
