Krijnen Eva A, van Dam Maureen, Bajrami Albulena, Bouman Piet M, Noteboom Samantha, Barkhof Frederik, Uitdehaag Bernard M J, Steenwijk Martijn D, Klawiter Eric C, Koubiyr Ismail, Schoonheim Menno M
MS Center Amsterdam, Department of Anatomy and Neurosciences, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Ann Clin Transl Neurol. 2025 Jan;12(1):121-136. doi: 10.1002/acn3.52261. Epub 2024 Dec 27.
To assess the interrelationship between cortical lesions and cortical thinning and volume loss in people with multiple sclerosis within cortical networks, and how this relates to future cognition.
In this longitudinal study, 230 people with multiple sclerosis and 60 healthy controls underwent 3 Tesla MRI at baseline and neuropsychological assessment at baseline and 5-year follow-up. Cortical regions (N = 212) were divided into seven functional networks. Regions were defined as either lesional or normal-appearing cortex based on presence of a cortical lesion on artificial intelligence-generated double inversion-recovery scans. Cortical volume and thickness were determined within lesional or normal-appearing cortex.
Prevalence of at least one cortical lesion was highest in the limbic (73%) followed by the default mode network (70.9%). Multiple sclerosis-related cortical thinning was more pronounced in lesional (mean Z-score = 0.70 ± 0.84) compared to normal-appearing cortex (-0.45 ± 0.60; P < 0.001) in all, except sensorimotor, networks. Cognitive dysfunction, particularly of verbal memory, visuospatial memory, and inhibition, at follow-up was best predicted by baseline network volume of normal-appearing cortex of the default mode network [B (95% CI) = 0.31 (0.18; 0.43), P < 0.001]. Mediation analysis showed that the effect of cortical lesions on future cognition was mediated by volume loss of the normal-appearing instead of lesional cortex, independent of white matter lesion volume.
Multiple sclerosis-related cortical thinning was worse in lesional compared to normal-appearing cortex, while volume loss of normal-appearing cortex was most predictive of subsequent cognitive decline, particularly in the default mode network. Mediation analyses indicate that cortical lesions impact cognitive decline plausibly by inducing atrophy, rather than through a direct effect.
评估皮质病变与皮质变薄及体积减少在多发性硬化症患者皮质网络中的相互关系，以及这与未来认知功能的关联。
在这项纵向研究中，230例多发性硬化症患者和60名健康对照者在基线时接受了3特斯拉磁共振成像（MRI）检查，并在基线和5年随访时进行了神经心理学评估。将212个皮质区域分为七个功能网络。根据人工智能生成的双反转恢复扫描上是否存在皮质病变，将区域定义为病变皮质或外观正常的皮质。在病变皮质或外观正常的皮质内测定皮质体积和厚度。
至少有一处皮质病变的患病率在边缘系统中最高（73%），其次是默认模式网络（70.9%）。除感觉运动网络外，在所有网络中，与多发性硬化症相关的皮质变薄在病变皮质中（平均Z值=0.70±0.84）比外观正常的皮质（-0.45±0.60；P<0.001）更为明显。随访时的认知功能障碍，尤其是言语记忆、视觉空间记忆和抑制功能障碍，最好由默认模式网络外观正常的皮质的基线网络体积预测[B（95%CI）=0.31（0.18；0.43），P<0.001]。中介分析表明，皮质病变对未来认知功能的影响是由外观正常而非病变皮质的体积减少介导的，与白质病变体积无关。
与外观正常的皮质相比，病变皮质中与多发性硬化症相关的皮质变薄更严重，而外观正常的皮质体积减少最能预测随后的认知衰退，尤其是在默认模式网络中。中介分析表明，皮质病变可能通过诱导萎缩而非直接作用影响认知衰退。
