Radboud University Medical Center, Department of Neurology (H.L., M.C., M.A.J., F.-E.d.L., A.M.T.), Donders Institute for Brain, Cognition and Behaviour, Nijmegen, the Netherlands.
Centre for Cognitive Neuroimaging, Radboud University (D.G.N., J.P.M., M.C.), Donders Institute for Brain, Cognition and Behaviour, Nijmegen, the Netherlands.
Stroke. 2023 May;54(5):1367-1376. doi: 10.1161/STROKEAHA.122.041687. Epub 2023 Mar 13.
Structural network damage is a potentially important mechanism by which cerebral small vessel disease (SVD) can cause cognitive impairment. As a central hub of the structural network, the role of thalamus in SVD-related cognitive impairments remains unclear. We aimed to determine the associations between the structural alterations of thalamic subregions and cognitive impairments in SVD.
In this cross-sectional study, 205 SVD participants without thalamic lacunes from the third follow-up (2020) of the prospective RUN DMC study (Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort), which was initiated in 2006, Nijmegen, were included. Cognitive functions included processing speed, executive function, and memory. Probabilistic tractography was performed from thalamus to 6 cortical regions, followed by connectivity-based thalamic segmentation to assess each thalamic subregion volume and connectivity (measured by mean diffusivity [MD] of the connecting white matter tracts) with the cortex. Least absolute shrinkage and selection operator regression analysis was conducted to identify the volumes or connectivity of the total thalamus and 6 thalamic subregions that have the strongest association with cognitive performance. Linear regression and mediation analyses were performed to test the association of least absolute shrinkage and selection operator-selected thalamic subregion volume or MD with cognitive performance, while adjusting for age and education.
We found that higher MD of the thalamic-motor tract was associated with worse processing speed (β=-0.27; <0.001), higher MD of the thalamic-frontal tract was associated with worse executive function (β=-0.24; =0.001), and memory (β=-0.28; <0.001), respectively. The mediation analysis showed that MD of thalamocortical tracts mediated the association between corresponding thalamic subregion volumes and the cognitive performances in 3 domains.
Our results suggest that the structural alterations of thalamus are linked to cognitive impairment in SVD, largely depending on the damage pattern of the white matter tracts connecting specific thalamic subregions and cortical regions.
结构网络损伤是脑小血管病（SVD）导致认知障碍的一种潜在重要机制。丘脑作为结构网络的中心枢纽，其在 SVD 相关认知障碍中的作用尚不清楚。我们旨在确定丘脑各亚区的结构改变与 SVD 认知障碍之间的相关性。
在这项横断面研究中，纳入了来自前瞻性 RUN DMC 研究（Radboud University Nijmegen Diffusion Tensor 和磁共振队列）的 205 名无丘脑腔隙的 SVD 患者（该研究于 2006 年启动，地点在奈梅亨）。这些患者来自该研究的第三次随访（2020 年）。认知功能包括处理速度、执行功能和记忆。进行了从丘脑到 6 个皮质区的概率性束追踪，然后进行基于连接的丘脑分割，以评估每个丘脑亚区的体积和与皮质的连接（通过连接白质束的平均弥散度 [MD] 来测量）。采用最小绝对收缩和选择算子回归分析确定与认知表现相关性最强的总丘脑和 6 个丘脑亚区的体积或连接。进行线性回归和中介分析，以测试最小绝对收缩和选择算子选择的丘脑亚区体积或 MD 与认知表现之间的关联，同时调整年龄和教育因素。
我们发现，丘脑-运动束的 MD 越高，与处理速度越差相关（β=-0.27；<0.001），丘脑-额束的 MD 越高，与执行功能越差相关（β=-0.24；=0.001），以及记忆越差（β=-0.28；<0.001）。中介分析表明，丘脑皮质束的 MD 介导了相应的丘脑亚区体积与 3 个认知领域的认知表现之间的关联。
我们的研究结果表明，丘脑的结构改变与 SVD 的认知障碍有关，这在很大程度上取决于连接特定丘脑亚区和皮质区的白质束的损伤模式。
