State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, China.
Key Laboratory of Health Technology Assessment of Fujian Province, School of Public Health, Xiamen University, Xiamen, China.
Int J Geriatr Psychiatry. 2024 Mar;39(3):e6079. doi: 10.1002/gps.6079.
To investigate the accuracy of longitudinal trajectories of blood biomarkers for predicting future onset of AD among MCI participants as well as to demonstrate dynamic prediction of the individual conversion risk applying joint modeling.
A total of 446 participants with MCI at baseline from the Alzheimer's Disease Neuroimaging Initiative database were included. We introduced joint modeling to analyze the effects of the longitudinal blood biomarkers on the conversion risk to AD, and further to build individual-specific prediction risk model.
During the follow-up, 345 participants remained with MCI and 101 progressed to AD, and were categorized as non-progression and progression group, respectively. Longitudinally, the positive association of the concentration dynamics of plasma p-tau181 and NfL with the conversion risk to AD from MCI was also demonstrated, with Hazard Ratio (HR) = 5.83 and HR = 4.18, respectively. When incorporating plasma p-tau181 and NfL together to predict AD progression, we observed improved performance (AUC = 0.701, Brier Score = 0.119). Two participants were chosen to exemplify the individual-specific risk prediction at different follow-up time for comparative analysis.
Plasma p-tau181 and NfL could serve as biomarkers for the prediction of AD onset, and the individualized prediction opens up the possibility to provide clinical information at a personal level.
探究血生物标志物纵向轨迹预测 MCI 患者 AD 发病的准确性，并通过联合建模展示个体转换风险的动态预测。
本研究纳入了阿尔茨海默病神经影像学倡议数据库中 446 名基线时患有 MCI 的参与者。我们引入联合建模来分析纵向血生物标志物对 AD 转化风险的影响，并进一步构建个体特异性预测风险模型。
在随访期间，345 名参与者仍患有 MCI，101 名进展为 AD，分别归类为非进展组和进展组。纵向分析显示，血浆 p-tau181 和 NfL 的浓度动态与 MCI 向 AD 的转化风险呈正相关，风险比（HR）分别为 5.83 和 4.18。当将血浆 p-tau181 和 NfL 一起纳入预测 AD 进展时，我们观察到了性能的改善（AUC=0.701，Brier 得分=0.119）。选择两名参与者在不同随访时间进行个体化风险预测，以进行比较分析。
血浆 p-tau181 和 NfL 可作为 AD 发病预测的生物标志物，个体化预测为提供个体化临床信息提供了可能。
