Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Neurobiol Aging. 2018 Apr;64:25-32. doi: 10.1016/j.neurobiolaging.2017.12.006. Epub 2017 Dec 16.
White matter hyperintensities (WMH) have been linked to cognitive dysfunction and dementia, although the reasons are unclear. One possibility is that WMH promote neurodegeneration, which, in turn, affects cognition. We examined whether cortical thickness, a marker of neurodegeneration, mediates the relationship between WMH and cognition among 519 older adults. Using conditional process analysis modeling techniques, we examined the association between WMH volume and global cognition and tested whether cortical thickness mediates this relationship statistically. We also tested specific regional hypotheses to determine whether cortical thickness or volume in the medial temporal lobe mediates the relationship between WMH volume and memory. Increased total WMH volume was associated with poorer global cognition and memory. Global cortical thickness and medial temporal lobe thickness/volume mediated the relationship of WMH volume on global cognition and memory functioning. The mediating relationship was similar across racial and ethnic groups and across diagnostic groups (i.e., mild cognitive impairment/Alzheimer's disease). The findings suggest that WMH promote atrophy, which, in turn, drives cognitive decline and highlight a potential pathway in which small vessel cerebrovascular disease affects cognition by promoting neurodegenerative changes directly.
脑白质高信号（WMH）与认知功能障碍和痴呆有关，尽管其原因尚不清楚。一种可能性是 WMH 促进神经退行性变，进而影响认知。我们研究了皮质厚度（神经退行性变的标志物）是否在 519 名老年人的 WMH 与认知之间的关系中起中介作用。我们使用条件过程分析模型技术，研究了 WMH 体积与整体认知之间的关联，并检验了皮质厚度是否可以从统计学上解释这种关系。我们还测试了特定的区域假设，以确定是皮质厚度还是内侧颞叶的厚度/体积介导了 WMH 体积与记忆之间的关系。总 WMH 体积的增加与整体认知和记忆功能较差有关。全脑皮质厚度和内侧颞叶厚度/体积介导了 WMH 体积与整体认知和记忆功能之间的关系。这种中介关系在不同种族和族裔群体以及不同的诊断群体（即轻度认知障碍/阿尔茨海默病）中是相似的。这些发现表明，WMH 促进了萎缩，而萎缩反过来又导致了认知能力的下降，并强调了小血管脑血管疾病通过直接促进神经退行性变化来影响认知的潜在途径。
