From the Department of Anatomy and Neurosciences (M.H., A.J.C.E., T.A.A.B., J.P., J.J.G.G., H.E.H., M.M.S.), Department of Neurology (I.D., B.M.J.U.), and Department of Radiology and Nuclear Medicine (I.D., F.B., A.-M.W.), MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, the Netherlands; and UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK.
Neurology. 2021 Aug 24;97(8):e794-e802. doi: 10.1212/WNL.0000000000012341. Epub 2021 Jun 7.
To characterize functional network changes related to conversion to cognitive impairment in a large sample of patients with multiple sclerosis (MS) over a period of 5 years.
Two hundred twenty-seven patients with MS and 59 healthy controls of the Amsterdam MS cohort underwent neuropsychological testing and resting-state fMRI at 2 time points (time interval 4.9 ± 0.9 years). At both baseline and follow-up, patients were categorized as cognitively preserved (CP; n = 123), mildly impaired (MCI; < -1.5 on ≥2 cognitive tests, n = 32), or impaired (CI; < -2 on ≥2 tests, n = 72), and longitudinal conversion between groups was determined. Network function was quantified with eigenvector centrality, a measure of regional network importance, which was computed for individual resting-state networks at both time points.
Over time, 18.9% of patients converted to a worse phenotype; 22 of 123 patients who were CP (17.9%) converted from CP to MCI, 10 of 123 from CP to CI (8.1%), and 12 of 32 patients with MCI converted to CI (37.5%). At baseline, default-mode network (DMN) centrality was higher in CI individuals compared to controls ( = 0.05). Longitudinally, ventral attention network (VAN) importance increased in CP, driven by stable CP and CP-to-MCI converters ( < 0.05).
Of all patients, 19% worsened in their cognitive status over 5 years. Conversion from intact cognition to impairment is related to an initial disturbed functioning of the VAN, then shifting toward DMN dysfunction in CI. Because the VAN normally relays information to the DMN, these results could indicate that in MS normal processes crucial for maintaining overall network stability are progressively disrupted as patients clinically progress.
在一个大型多发性硬化症（MS）患者样本中，在 5 年的时间内，描述与认知障碍转化相关的功能网络变化。
阿姆斯特丹 MS 队列的 227 名 MS 患者和 59 名健康对照者在 2 个时间点（时间间隔 4.9±0.9 年）接受神经心理学测试和静息态 fMRI。在基线和随访时，患者被分为认知正常（CP；n=123）、轻度认知障碍（MCI；≥2 项认知测试得分低于-1.5，n=32）或认知障碍（CI；≥2 项测试得分低于-2，n=72），并确定组间的纵向转换。网络功能通过特征向量中心度来量化，这是一种衡量区域网络重要性的指标，它是在两个时间点计算个体静息态网络的。
随着时间的推移，18.9%的患者出现了更差的表型；123 名 CP 患者中有 22 名（17.9%）从 CP 转为 MCI，123 名 CP 中有 10 名（8.1%）转为 CI，32 名 MCI 中有 12 名（37.5%）转为 CI。基线时，与对照组相比，CI 患者的默认模式网络（DMN）中心度更高（ = 0.05）。纵向来看，CP 中腹侧注意网络（VAN）的重要性增加，这是由稳定的 CP 和 CP 向 MCI 转化驱动的（ < 0.05）。
在所有患者中，19%的患者在 5 年内认知状态恶化。从完整认知到损伤的转变与 VAN 的初始功能障碍有关，然后在 CI 中转向 DMN 功能障碍。由于 VAN 通常将信息传递给 DMN，这些结果可能表明，在 MS 中，维持整体网络稳定性的正常过程随着患者的临床进展而逐渐受到破坏。
