Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Department of Internal Medicine, Section of Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Cogn Affect Behav Neurosci. 2024 Dec;24(6):1121-1140. doi: 10.3758/s13415-024-01219-3. Epub 2024 Sep 20.
White matter hyperintensities (WMHs) are associated with age-related cognitive impairment and increased risk of Alzheimer's disease. However, the manner by which WMHs contribute to cognitive impairment is unclear. Using a combination of predictive modeling and network neuroscience, we investigated the relationship between structural white matter connectivity and age, fluid cognition, and WMHs in 68 healthy adults (18-78 years). Consistent with previous work, WMHs were increased in older adults and exhibited a strong negative association with fluid cognition. Extending previous work, using predictive modeling, we demonstrated that age, WMHs, and fluid cognition were jointly associated with widespread alterations in structural connectivity. Subcortical-cortical connections between the thalamus/basal ganglia and frontal and parietal regions of the default mode and frontoparietal networks were most prominent. At the network level, both age and WMHs were negatively associated with network density and communicability, and positively associated with modularity. Spatially, WMHs were most prominent in arterial zones served by the middle cerebral artery and associated lenticulostriate branches that supply subcortical regions. Finally, WMHs overlapped with all major white matter tracts, most prominently in tracts that facilitate subcortical-cortical communication and are implicated in fluid cognition, including the anterior thalamic-radiations and forceps minor. Finally, results of mediation analyses suggest that whole-brain WMH load influences age-related decline in fluid cognition. Thus, across multiple levels of analysis, we showed that WMHs were increased in older adults and associated with altered structural white matter connectivity and network topology involving subcortical-cortical pathways critical for fluid cognition.
脑白质高信号（WMHs）与年龄相关的认知障碍和阿尔茨海默病风险增加有关。然而，WMHs 导致认知障碍的方式尚不清楚。本研究采用预测建模和网络神经科学相结合的方法，在 68 名健康成年人（18-78 岁）中，调查了结构白质连接与年龄、流体认知和 WMH 之间的关系。与之前的研究一致，WMHs 在老年人中增加，并与流体认知呈强烈的负相关。通过预测建模，我们扩展了之前的研究，表明年龄、WMHs 和流体认知与结构连接的广泛改变有关。丘脑/基底节与默认模式和额顶网络的额顶区域之间的皮质下皮质连接最为明显。在网络层面，年龄和 WMHs 与网络密度和连通性呈负相关，与模块性呈正相关。从空间上看，WMHs 主要出现在大脑中动脉及其供应皮质下区域的纹状体分支供应的动脉区。最后，WMHs 与所有主要的白质束重叠，与促进皮质下皮质通讯并与流体认知有关的束，包括前丘脑辐射和小内囊纤维最为明显。最后，中介分析的结果表明，全脑 WMH 负荷影响与年龄相关的流体认知下降。因此，在多个分析层面上，我们表明，WMHs 在老年人中增加，并与改变的结构白质连接和网络拓扑有关，涉及对流体认知至关重要的皮质下皮质通路。
