Charisis Sokratis, Rashid Tanweer, Dintica Christina, Gonzales Mitzi, Liu Hangfan, Ware Jeffrey B, Austin Thomas R, Jensen Paul N, Fohner Alison E, Tanley Jordan E, Ding Jingzhong, Luchsinger José A, Sachs Bonnie, Nasrallah Ilya M, Bryan R Nick, Hayden Kathleen M, Wolk David, Rascovsky Katya, Davatzikos Christos, Longstreth William T, Yaffe Kristine, Seshadri Sudha, Heckbert Susan R, Hughes Timothy, Habes Mohamad
Neuroimage Analytics Laboratory (NAL) and the Biggs Institute Neuroimaging Core (BINC), Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health Science Center San Antonio, San Antonio, Texas, USA.
Department of Neurology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Alzheimers Dement. 2025 Jun;21(6):e70326. doi: 10.1002/alz.70326.
We aimed to examine the global impact of brain small vessel disease (SVD) on cognitive performance.
In 892 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), we derived perivascular spaces (PVS), white matter hyperintensities (WMH), microbleeds (MB), and white matter fractional anisotropy (FA) and trace (TR). Cognitive function was assessed with a comprehensive neuropsychological battery.
A composite SVD measure was constructed as a linear combination of basal ganglia PVS, thalamus PVS, periventricular WMH, subcortical WMH, and white matter FA and TR, and exhibited associations with worse global and domain-specific cognitive performance. Additionally, SVD mediated the effect of age and cardiovascular disease risk on global cognitive function, both directly and through smaller gray matter (GM) volume.
Integrating multiple individual SVD endophenotypes may more accurately reflect the neurobiology of SVD and capture its global impact on cognition. SVD mediates the effects of age and cardiovascular disease risk on cognition through both atrophy-related and non-atrophy-related pathways.
Associations between individual magnetic resonance imaging (MRI) markers of brain small vessel disease and cognitive outcomes might not fully capture the global impact of small vessel disease on cognition. We modeled small vessel disease as a latent construct, integrating multiple MRI endophenotypes in strategic brain regions. The small vessel disease construct was associated with worse global and domain-specific cognitive performance. The small vessel disease construct exhibited mediating effects in the relationships of aging and cardiovascular disease risk with cognition through pathways that both involve and are independent of brain atrophy. Integrating information from multiple relevant imaging endophenotypes could open new avenues in small vessel disease research, broadening our understanding of its risk factors and clinical correlates.
我们旨在研究脑小血管疾病（SVD）对认知功能的全球影响。
在动脉粥样硬化多族裔研究（MESA）的892名参与者中，我们得出了血管周围间隙（PVS）、白质高信号（WMH）、微出血（MB）以及白质分数各向异性（FA）和迹线（TR）。使用综合神经心理测试组评估认知功能。
构建了一个复合SVD测量指标，作为基底节PVS、丘脑PVS、脑室周围WMH、皮质下WMH以及白质FA和TR的线性组合，并显示出与较差的整体和特定领域认知功能相关。此外，SVD直接并通过较小的灰质（GM）体积介导了年龄和心血管疾病风险对整体认知功能的影响。
整合多个个体SVD内表型可能更准确地反映SVD的神经生物学特性，并捕捉其对认知的全球影响。SVD通过与萎缩相关和与萎缩无关的途径介导年龄和心血管疾病风险对认知的影响。
脑小血管疾病的个体磁共振成像（MRI）标记与认知结果之间的关联可能无法完全捕捉小血管疾病对认知的全球影响。我们将小血管疾病建模为一个潜在结构，整合了战略脑区的多个MRI内表型。小血管疾病结构与较差的整体和特定领域认知功能相关。小血管疾病结构在衰老和心血管疾病风险与认知的关系中通过涉及和独立于脑萎缩的途径表现出中介作用。整合来自多个相关成像内表型的信息可能为小血管疾病研究开辟新途径，拓宽我们对其危险因素和临床相关性的理解。
