Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee, United States of America.
PLoS One. 2020 Oct 16;15(10):e0240513. doi: 10.1371/journal.pone.0240513. eCollection 2020.
In vivo functional changes in white matter during the progression of Alzheimer's disease (AD) have not been previously reported. Our objectives are to measure changes in white matter functional connectivity (FC) in an elderly population undergoing cognitive decline as AD develops, to establish their relationship to neuropsychological scores of cognitive abilities, and to assess the performance in prediction of AD using white matter FC measures as features.
Analyses were conducted using resting state functional MRI and neuropsychological data from 383 ADNI participants, including 136 cognitive normal (CN) controls, 46 with significant memory concern, 83 with early mild cognitive impairment (MCI), 37 with MCI, 46 with late MCI, and 35 with AD dementia. FC metrics between segregated white matter tracts and discrete gray matter volumes or between white matter tracts were quantitatively analyzed and characterized, along with their relationships to 6 cognitive measures. Finally, supervised machine learning was implemented on white matter FCs to classify the participants and performance of the classification was evaluated.
Significant decreases in FC measures were found in white matter with prominent, specific, regional deficits appearing in late MCI and AD dementia patients from CN. These changes significantly correlated with neuropsychological measurements of impairments in cognition and memory. The sensitivity and specificity of distinguishing AD dementia and CN using white matter FCs were 0.83 and 0.81 respectively.
The white matter FC decreased in late MCI and AD dementia patients compared to CN participants, and this decrease was correlated with cognitive measures. White matter FC is valuable in the prediction of AD. All these findings suggest that white matter FC may be a promising avenue for understanding functional impairments in white matter tracts during AD progression.
以前没有报道过阿尔茨海默病（AD）进展过程中白质的体内功能变化。我们的目的是测量认知能力下降的老年人群中白质功能连接（FC）的变化，确定其与认知能力神经心理学评分的关系，并评估使用白质 FC 测量作为特征对 AD 的预测性能。
使用 ADNI 383 名参与者的静息状态功能磁共振成像和神经心理学数据进行分析，包括 136 名认知正常（CN）对照者、46 名有明显记忆问题者、83 名早期轻度认知障碍（MCI）者、37 名 MCI 者、46 名晚期 MCI 者和 35 名 AD 痴呆者。定量分析和描述了分离的白质束和离散灰质体积之间或白质束之间的 FC 度量，以及它们与 6 种认知测量的关系。最后，在白质 FC 上实施了有监督的机器学习，以对参与者进行分类，并评估分类的性能。
与 CN 相比，晚期 MCI 和 AD 痴呆患者的白质 FC 测量值显著降低，白质出现明显、特定、区域性缺陷。这些变化与认知和记忆障碍的神经心理学测量显著相关。使用白质 FC 区分 AD 痴呆和 CN 的敏感性和特异性分别为 0.83 和 0.81。
与 CN 参与者相比，晚期 MCI 和 AD 痴呆患者的白质 FC 降低，并且这种降低与认知测量相关。白质 FC 对白质 FC 具有预测 AD 的价值。所有这些发现表明，白质 FC 可能是理解 AD 进展过程中白质束功能障碍的有前途的途径。
