Bioengineering Department, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Ranica, BG, Italy.
Department of Neuroradiology, ASST Papa Giovanni XXIII, Bergamo, Italy.
Ann Clin Transl Neurol. 2024 Sep;11(9):2457-2472. doi: 10.1002/acn3.52164. Epub 2024 Jul 30.
The aim of this study was to assess COVID-19-related gray matter (GM) structural alterations in two distinct groups of patients presenting with the prevailing and distinctive COVID-19-related neurological symptoms - isolated olfactory disorders as sole neurological manifestation (COVID-OD) and cognitive disorders (COVID-CD) - as compared to a control group of unaffected individuals.
The study included 61 COVID-CD patients (57 [60-63] years, 62% females), 84 COVID-OD patients (49 [35-57] years, 60% females), and 17 controls (51 [41-52] years, 41% females). Region-based morphometry (RBM) and voxel-based morphometry (VBM) were performed on T1-weighted MRI scans to assess GM regional volume and voxel-wise density differences between COVID-19 patients and controls. Surface-based morphometry (SBM) was applied to investigate cortical thickness alterations. The statistical models built to assess GM structural differences among groups included total intracranial volume and age as nuisance variables.
The multi-morphometric analysis revealed statistically significant (p < 0.05 corrected for multiple comparisons) reduction in GM regional volumes, in voxel-wise GM density and in cortical thickness in both COVID-CD and COVID-OD patient groups as compared to controls. Across all three analyses, COVID-CD patients showed more distributed and severe GM loss than COVID-OD patients. The most prominently affected GM regions in the COVID-CD group included the hippocampus, putamen, cingulate gyrus, precuneus, precentral and postcentral gyri, amygdala, lingual gyrus, and caudate nucleus.
Our MRI findings show that COVID-19-related olfactory and cognitive disorders both induce GM atrophy, although at different degrees of severity, likely indicative of neurodegeneration and neuroinflammation.
本研究旨在评估具有不同 COVID-19 相关神经系统症状表现的两组患者的大脑灰质（GM）结构变化，这些症状表现为孤立性嗅觉障碍（COVID-OD）和认知障碍（COVID-CD），这两种症状是 COVID-19 的主要和独特的神经症状，与未受影响的对照组进行比较。
本研究纳入了 61 名 COVID-CD 患者（57 [60-63] 岁，62%为女性）、84 名 COVID-OD 患者（49 [35-57] 岁，60%为女性）和 17 名对照组参与者（51 [41-52] 岁，41%为女性）。我们对 T1 加权 MRI 扫描进行了基于体素的形态计量学（VBM）和基于区域的形态计量学（RBM）分析，以评估 GM 区域体积和 GM 密度的差异。我们还应用了表面形态计量学（SBM）来研究皮质厚度的变化。为了评估组间 GM 结构差异，我们构建了统计学模型，其中包括总颅内体积和年龄作为干扰变量。
多形态计量分析显示，与对照组相比，COVID-CD 和 COVID-OD 患者的 GM 区域体积、GM 密度和皮质厚度均存在统计学上显著的（p < 0.05，经多重比较校正）减少。在所有三种分析中，COVID-CD 患者的 GM 损失比 COVID-OD 患者更广泛且严重。在 COVID-CD 组中，受影响最严重的 GM 区域包括海马体、壳核、扣带回、楔前叶、中央前回和中央后回、杏仁核、舌回和尾状核。
我们的 MRI 研究结果表明，COVID-19 相关的嗅觉和认知障碍均会引起 GM 萎缩，尽管严重程度不同，可能提示存在神经退行性变和神经炎症。
