Tang Chao, Ding Yaqi, Yang Jiaxin, He Dian
Department of Neurology, Affiliated Hospital of Guizhou Medical University, Guiyang 550000, Guizhou Province, China.
Department of Neurology, Affiliated Hospital of Guizhou Medical University, Guiyang 550000, Guizhou Province, China.
J Prev Alzheimers Dis. 2025 Sep;12(8):100209. doi: 10.1016/j.tjpad.2025.100209. Epub 2025 May 29.
The co-occurrence of Alzheimer's disease and cerebrovascular disease is increasingly prevalent in aging populations, yet the mechanisms of their interaction remain incompletely understood. This study aims to investigate the associations between CVD and AD and their composite effects on cognitive function, identifying key mediating pathways in these relationships.
Participants underwent standardized clinical evaluations, detailed neuropsychological testing, and comprehensive neuropathological examinations. Structural equation modeling with multiple mediation analyses was employed to disentangle direct and indirect effects of vascular pathology on cognition and identify key mediating pathways. Relationships between specific cognitive domain assessments and whole brain and hippocampal volumes were analyzed, while interactions between traditional AD biomarkers (amyloid, tau) and vascular factors were examined.
CVD substantially increased AD risk. Structural equation modeling revealed that vascular factors influence cognitive performance primarily through hippocampal atrophy, APOE genotype, and cerebral atrophy. Participants with concomitant AD +CVD pathology displayed a distinctive hybrid pattern of brain-cognition relationships, with stronger correlations between hippocampal atrophy and cognitive performance compared to pure AD or CVD cases. Pathway-specific analysis demonstrated that hippocampal atrophy served as the strongest mediator of vascular effects on cognition, followed by cerebral atrophy and APOE genotype.
Our findings demonstrate that cerebrovascular disease significantly increases the risk of Alzheimer's disease and substantially influences its clinical expression through multiple pathways, with structural brain changes serving as critical mediators of vascular effects on cognition. These results highlight the importance of addressing vascular health as an integral component of strategies to prevent and treat Alzheimer's disease and related cognitive disorders.
阿尔茨海默病与脑血管疾病的共现现象在老年人群中日益普遍，但其相互作用机制仍未完全明确。本研究旨在探讨心血管疾病（CVD）与阿尔茨海默病（AD）之间的关联及其对认知功能的综合影响，确定这些关系中的关键中介途径。
参与者接受了标准化临床评估、详细的神经心理学测试和全面的神经病理学检查。采用具有多重中介分析的结构方程模型来剖析血管病理学对认知的直接和间接影响，并确定关键中介途径。分析了特定认知领域评估与全脑及海马体积之间的关系，同时研究了传统AD生物标志物（淀粉样蛋白、tau蛋白）与血管因素之间的相互作用。
CVD显著增加了AD风险。结构方程模型显示，血管因素主要通过海马萎缩、APOE基因型和脑萎缩影响认知表现。伴有AD + CVD病理学特征的参与者表现出独特的脑 - 认知关系混合模式，与单纯AD或CVD病例相比，海马萎缩与认知表现之间的相关性更强。特定途径分析表明，海马萎缩是血管对认知影响的最强中介因素，其次是脑萎缩和APOE基因型。
我们的研究结果表明，脑血管疾病显著增加了阿尔茨海默病的风险，并通过多种途径实质性地影响其临床表型，脑结构变化是血管对认知影响的关键中介因素。这些结果凸显了将解决血管健康问题作为预防和治疗阿尔茨海默病及相关认知障碍策略的一个组成部分的重要性。
