摘要
背景:轻度认知障碍(MCI)通常先于痴呆的症状期,构成了预防性治疗的机会之窗。目的:本研究的目的是预测MCI患者达到痴呆的时间,并获得MCI向痴呆发展的最可能的自然史。 方法:本研究对来自阿尔茨海默病神经影像学倡议(ADNI)队列的633名MCI患者和145名痴呆患者进行了为期15年的4726次访问。结合基线AT(N)剖面数据和纵向预测模型进行了应用。提出了一种结合监督学习和非监督学习的认知衰退进展分类诊断预测和时间线估计的数据驱动方法。 结果:选择了仅神经心理学测量的简化向量来训练模型。在基线时,这种方法在检测未来几年从轻度认知障碍转变为痴呆的高风险受试者方面表现优异。此外,还建立了疾病进展模型(DPM),并使用三个指标进行了验证。由于DPM聚焦于研究人群,推断淀粉样蛋白病理(a +)出现在痴呆前约7年,tau病理(T+)和神经变性(N+)几乎同时发生,在痴呆前3至4年之间。此外,与MCI-A受试者相比,MCI-A+受试者进展到痴呆的速度更快。 结论:基于提出的自然病史和AD标志物的横断面和纵向分析,结果表明,在AD前驱期只需要一次脑脊液样本。从轻度认知障碍到痴呆及其时间表的预测只能通过神经心理学测量来实现。
关键词: 轻度认知障碍,阿尔茨海默病,AT(N)生物标志物,预测模型,疾病进展模型,痴呆。
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