Department of Neurology, University Hospital of Cologne, Cologne 50937, Germany; Department of General, Abdominal, Endocrine and Minimally Invasive Surgery, Academic Hospital Bogenhausen, 81925 Munich, Germany.
Department of Neurology, University Hospital of Cologne, Cologne 50937, Germany; Cognitive Neuroscience, Institute of Neuroscience and Medicine (INM-3), Research Centre, Jülich 52428, Germany.
Neuroimage Clin. 2018 Jun 18;19:948-962. doi: 10.1016/j.nicl.2018.06.016. eCollection 2018.
In recent years, changes in resting-state networks (RSN), identified by functional magnetic resonance imaging (fMRI), have gained increasing attention as potential biomarkers and trackers of neurological disorders such as Alzheimer's disease (AD). Intersession reliability of RSN is fundamental to this approach. In this study, we investigated the test-retest reliability of three memory related RSN (i.e., the default mode, salience, and executive control network) in 15 young, 15 healthy seniors (HS), and 15 subjects affected by mild cognitive impairment (MCI) with positive biomarkers suggestive of incipient AD (6 females each). FMRI was conducted on three separate occasions. Independent Component Analysis decomposed the resting-state data into RSNs. Comparisons of variation in functional connectivity between groups were made applying different thresholds in an explorative approach. Intersession test-retest reliability was evaluated by intraclass correlation coefficient (ICC) comparisons. To assess the effect of gray matter volume loss, motion, cerebrospinal fluid based biomarkers and the time gap between sessions on intersession variation, the former four were correlated separately with the latter. Data showed that i) young subjects ICCs (relative to HS/MCI-subjects) had higher intersession reliability, ii) stringent statistical thresholds need to be applied to prevent false-positives, iii) both HS and MCI-subjects (relative to young) showed significantly more clusters of intersession variation in all three RSN, iv) while intersession variation was highly correlated with head motion, it was also correlated with biomarkers (especially phospho-tau), the time gap between sessions and local GMV. Results indicate that time gaps between sessions should be kept constant and that head motion must be taken into account when using RSN to assess aging and neurodegeneration. In patients with prodromal AD, re-test reliability may be increased by accouting for overall disease burden by including biomarkers of neuronal injury (especially phospho-tau) in statistical analyses. Local atrophy however, does not seem to play a major role in regards to reliability, but should be used as covariate depending on the research question.
近年来，通过功能磁共振成像（fMRI）识别的静息态网络（RSN）的变化作为阿尔茨海默病（AD）等神经退行性疾病的潜在生物标志物和跟踪器越来越受到关注。RSN 的组内测试重测信度是这种方法的基础。在这项研究中，我们调查了 15 名年轻、15 名健康老年人（HS）和 15 名轻度认知障碍（MCI）伴有提示 AD 早期生物标志物的受试者（每组 6 名女性）中三种与记忆相关的 RSN（即默认模式、突显和执行控制网络）的测试重测信度。在三个不同的时间点进行 fMRI。通过探索性方法，应用不同的阈值比较组间功能连接的变化。通过组内相关系数（ICC）比较评估组内测试重测信度。为了评估灰质体积损失、运动、基于脑脊液的生物标志物和两次扫描之间的时间间隔对组内变化的影响，将前四个因素分别与后一个因素相关联。结果显示：i）与 HS/MCI 受试者相比，年轻受试者的 ICC（相对于 HS/MCI 受试者）具有更高的组内测试重测信度；ii）需要应用严格的统计阈值以防止假阳性；iii）与年轻受试者相比，HS 和 MCI 受试者在所有三个 RSN 中均显示出更多的组内变化簇；iv）尽管组内变化与头部运动高度相关，但它也与生物标志物（尤其是磷酸化 tau）、两次扫描之间的时间间隔和局部 GMV 相关。结果表明，两次扫描之间的时间间隔应保持恒定，在使用 RSN 评估衰老和神经退行性变时，必须考虑头部运动。在有前驱 AD 的患者中，通过在统计分析中纳入神经元损伤的生物标志物（尤其是磷酸化 tau）来考虑整体疾病负担，可能会增加重测的可靠性。然而，局部萎缩似乎在可靠性方面没有起到主要作用，但应根据研究问题用作协变量。
