痴呆症发病的估计:轻度认知障碍患者的 AT(N) 图谱和预测模型

Carlos Platero, Jussi Tohka, Bryan Strange
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引用次数: 0

摘要

背景:轻度认知障碍(MCI)通常早于痴呆症的症状期,是预防性疗法的机会之窗:本研究的目的是预测 MCI 患者达到痴呆的剩余时间,并获得 MCI 向痴呆发展过程中最有可能出现的自然病史:这项研究的对象是阿尔茨海默病神经影像学倡议(ADNI)队列中的633名MCI患者和145名痴呆症患者,他们在15年间共就诊4726次。研究结合了基线AT(N)特征数据和纵向预测模型。结合监督和非监督学习技术,提出了一种数据驱动的方法,用于分类诊断预测和认知能力下降进程的时间轴估计:结果:在训练模型时,只选择了神经心理测量的缩减向量。在基线阶段,这种方法在检测未来几年从 MCI 转为痴呆症的高风险受试者方面表现出色。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。根据以研究人群为重点的 DPM,推断出淀粉样病变(A+)出现在痴呆症出现前 7 年左右,而 tau 病变(T+)和神经变性(N+)几乎同时出现,即在痴呆症出现前 3 到 4 年之间。此外,与MCI-A-受试者相比,MCI-A+受试者发展为痴呆症的速度更快:结论:根据所提出的自然病史以及对AD标记物的横断面和纵向分析,结果表明在AD的前驱阶段只需采集一份脑脊液样本。从 MCI 到痴呆的预测及其时间表完全可以通过神经心理测量来实现。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Estimating Dementia Onset: AT(N) Profiles and Predictive Modeling in Mild Cognitive Impairment Patients.

Background: Mild Cognitive Impairment (MCI) usually precedes the symptomatic phase of dementia and constitutes a window of opportunities for preventive therapies.

Objectives: The objective of this study was to predict the time an MCI patient has left to reach dementia and obtain the most likely natural history in the progression of MCI towards dementia.

Methods: This study was conducted on 633 MCI patients and 145 subjects with dementia through 4726 visits over 15 years from Alzheimer Disease Neuroimaging Initiative (ADNI) cohort. A combination of data from AT(N) profiles at baseline and longitudinal predictive modeling was applied. A data-driven approach was proposed for categorical diagnosis prediction and timeline estimation of cognitive decline progression, which combined supervised and unsupervised learning techniques.

Results: A reduced vector of only neuropsychological measures was selected for training the models. At baseline, this approach had high performance in detecting subjects at high risk of converting from MCI to dementia in the coming years. Furthermore, a Disease Progression Model (DPM) was built and also verified using three metrics. As a result of the DPM focused on the studied population, it was inferred that amyloid pathology (A+) appears about 7 years before dementia, and tau pathology (T+) and neurodegeneration (N+) occur almost simultaneously, between 3 and 4 years before dementia. In addition, MCI-A+ subjects were shown to progress more rapidly to dementia compared to MCI-A- subjects.

Conclusion: Based on proposed natural histories and cross-sectional and longitudinal analysis of AD markers, the results indicated that only a single cerebrospinal fluid sample is necessary during the prodromal phase of AD. Prediction from MCI into dementia and its timeline can be achieved exclusively through neuropsychological measures.

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