Hobden Georgina, Reid Graham, Chiesa Scott T, Wang Congxiyu, Jobbins Lucy, Mackay Clare E, Hughes Alun D, Ebmeier Klaus P, Pitt Jemma, Kivimäki Mika, Singh-Manoux Archana, Suri Sana
Department of Experimental Psychology, University of Oxford, Oxford, UK.
Department of Psychiatry, University of Oxford, Oxford, United Kingdom.
BMC Med. 2025 Jun 3;23(1):330. doi: 10.1186/s12916-025-04105-y.
Cardiovascular disease has been associated with an increased dementia risk, but the underlying mechanisms for this heart-brain link are unclear. This study sought to examine associations between aortic and carotid artery structure with cerebrovascular reactivity (CVR), white matter hyperintensities (WMHs), and cognition in later-life.
One hundred sixty three participants (25.8% female) from the Whitehall II Imaging cohort completed two examinations (M ± SD age 68.2 ± 4.4 at Wave-1 and 76.9 ± 4.5 at Wave-2) of neuropsychological assessments and 3T brain magnetic resonance imaging (MRI) FLAIR scans to quantify WMHs. Wave-2 additionally included vascular sonography of the aorta and carotid artery, and 3T functional MRI scans to measure CVR (mean % change BOLD signal change during a CO challenge). Wave-2 factor scores of aortic and carotid arterial diameters, stiffness, and compliance were the exposure variables. Midlife Framingham Cardiovascular Risk Score (FRS) measured before Wave-1 was a potential effect modifier. WMH volume, grey matter CVR, cognitive factor scores (episodic memory, working memory, executive function, visuospatial memory, fluency, lexical retrieval) at Wave-2, and changes in WMH and cognition between Wave-1 and Wave-2 were used as outcome variables.
Larger aortic diameter (ß = 0.38, SE = 0.11) and greater aortic stiffness (ß = 0.27, SE = 0.10) were associated with larger carotid diameter, independently of body size. Higher midlife FRS was associated with larger aortic and carotid diameters and increased carotid stiffness in old age. We observed notable artery-brain associations, such that larger aortic (ß = 0.17, SE = 0.06) and carotid diameters (ß = 0.11, SE = 0.05) were associated with larger WMH lesion volumes at Wave-2. Larger aortic diameter (ß = 0.08 SE = 0.03) and lower carotid compliance (ß = - 0.06, SE = 0.02) at Wave-2 were also associated with greater longitudinal increases in WMH volumes over the preceding 9 years. Higher stiffness and lower compliance of the aorta and carotid were associated with worse cognitive outcomes across a range of domains, and these associations were moderated by midlife FRS. Larger carotid diameter was associated with higher cerebrovascular reactivity (ß = 0.02, SE = 0.01), suggesting a potential compensatory pathway.
Adverse structural and functional changes in the aorta and carotid artery were inter-related and associated with vascular brain lesions, cerebrovascular reactivity, and poorer cognitive outcomes in older age.
心血管疾病与痴呆风险增加有关，但这种心脑联系的潜在机制尚不清楚。本研究旨在探讨主动脉和颈动脉结构与脑血管反应性（CVR）、白质高信号（WMH）及晚年认知之间的关联。
来自白厅II影像队列的163名参与者（25.8%为女性）完成了两次检查（第一次检查时年龄M±SD为68.2±4.4岁，第二次检查时为76.9±4.5岁），包括神经心理学评估以及3T脑磁共振成像（MRI）液体衰减反转恢复（FLAIR）扫描以量化WMH。第二次检查还包括主动脉和颈动脉的血管超声检查，以及3T功能MRI扫描以测量CVR（CO刺激期间BOLD信号变化的平均百分比变化）。主动脉和颈动脉直径、僵硬度及顺应性的第二次检查因子得分作为暴露变量。第一次检查前测量的中年弗雷明汉心血管风险评分（FRS）是一个潜在的效应修饰因素。第二次检查时的WMH体积、灰质CVR、认知因子得分（情景记忆、工作记忆、执行功能、视觉空间记忆、流畅性、词汇检索），以及第一次检查和第二次检查之间WMH和认知的变化用作结局变量。
较大的主动脉直径（β = 0.38，标准误 = 0.11）和较高的主动脉僵硬度（β = 0.27，标准误 = 0.10）与较大的颈动脉直径相关，与体型无关。较高的中年FRS与老年时较大的主动脉和颈动脉直径及增加了的颈动脉僵硬度相关。我们观察到显著的动脉与脑的关联，即较大的主动脉（β = 0.17，标准误 = 0.06）和颈动脉直径（β = 0.11，标准误 = 0.05）与第二次检查时较大的WMH病变体积相关。第二次检查时较大的主动脉直径（β = 0.08，标准误 = 0.03）和较低的颈动脉顺应性（β = -0.06，标准误 = 0.02）也与之前9年中WMH体积更大幅度的纵向增加相关。主动脉和颈动脉较高的僵硬度及较低的顺应性与一系列领域中较差的认知结局相关，并且这些关联受到中年FRS的调节作用影响。较大的颈动脉直径与较高的脑血管反应性相关（β = 0.02，标准误 = 0.01），提示一条潜在的代偿途径。
主动脉和颈动脉的不良结构和功能变化相互关联，并与老年时的血管性脑病变、脑血管反应性及较差的认知结局相关。
