Ackah Joseph A, Li Xuelong, Zeng Huixing, Chen Xiangyan
Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong SAR, China.
Department of Neurology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
Behav Brain Funct. 2025 Apr 22;21(1):12. doi: 10.1186/s12993-025-00274-1.
Cerebral large artery and small vessel diseases are considered substrates of neurological disorders. We explored how the mechanisms of neurovascular uncoupling, dysfunctional blood-brain-barrier (BBB), compromised glymphatic pathway, and impaired cerebrovascular reactivity (CVR) and autoregulation, identified through diverse neuroimaging techniques, impact cerebral large artery and small vessel diseases.
Studies (1990-2024) that reported on neuroradiological findings on ageing-related cerebral large artery and small vessel diseases were reviewed. Fifty-two studies involving 23,693 participants explored the disease mechanisms, 9 studies (sample size = 3,729) of which compared metrics of cerebrovascular functions (CF) between participants with cerebral large artery and small vessel diseases (target group) and controls with no vascular disease. Measures of CF included CVR, cerebral blood flow (CBF), blood pressure and arterial stiffness.
The findings from 9 studies (sample size = 3,729, mean age = 60.2 ± 11.5 years), revealed negative effect sizes of CVR [SMD = - 1.86 (95% CI - 2.80, - 0.92)] and CBF [SMD = - 2.26 (95% CI - 4.16, - 0.35)], respectively indicating a reduction in cerebrovascular functions in the target group compared to their controls. Conversely, there were significant increases in the measures of blood pressure [SMD = 0.32 (95% CI 0.18, 0.46)] and arterial stiffness [SMD = 0.87 (95% CI 0.77, 0.98)], which signified poor cerebrovascular functions in the target group. In the combined model the overall average effect size was negative [SMD = - 0.81 (95% CI - 1.53 to - 0.08), p < 0.001]. Comparatively, this suggests that the negative impacts of CVR and CBF reductions significantly outweighed the effects of blood pressure and arterial stiffness, thereby predominantly shaping the overall model. Against their controls, trends of reduction in CF were observed exclusively among participants with cerebral large artery disease (SMD = - 2.09 [95% CI: - 3.57, - 0.62]), as well as those with small vessel diseases (SMD = - 0.85 [95% CI - 1.34, - 0.36]). We further delineated the underlying mechanisms and discussed their interconnectedness with cognitive impairments.
In a vicious cycle, dysfunctional mechanisms in the glymphatic system, neurovascular unit, BBB, autoregulation, and reactivity play distinct roles that contribute to reduced CF and cognitive risk among individuals with cerebral large artery and/or small vessel diseases. Reduction in CVR and CBF points to reductions in CF, which is associated with increased risk of cognitive impairment among ageing populations ≥ 60 years.
大脑大动脉和小血管疾病被认为是神经系统疾病的基础。我们探讨了通过多种神经影像学技术确定的神经血管解偶联、血脑屏障（BBB）功能障碍、淋巴系统途径受损以及脑血管反应性（CVR）和自动调节受损的机制如何影响大脑大动脉和小血管疾病。
对1990年至2024年期间报告的与衰老相关的大脑大动脉和小血管疾病神经放射学研究结果进行了综述。52项涉及23693名参与者的研究探讨了疾病机制，其中9项研究（样本量=3729）比较了大脑大动脉和小血管疾病参与者（目标组）与无血管疾病对照组之间的脑血管功能（CF）指标。CF的测量包括CVR、脑血流量（CBF）、血压和动脉僵硬度。
9项研究（样本量=3729，平均年龄=60.2±11.5岁）的结果显示，CVR [标准化均数差（SMD）=-1.86（95%可信区间-2.80，-0.92）]和CBF [SMD=-2.26（95%可信区间-4.16，-0.35）]的效应量为负，分别表明目标组的脑血管功能与对照组相比有所下降。相反，血压[SMD=0.32（95%可信区间0.18，0.46）]和动脉僵硬度[SMD=0.87（95%可信区间0.77，0.98）]的测量值显著增加，这表明目标组的脑血管功能较差。在综合模型中，总体平均效应量为负[SMD=-0.81（95%可信区间-1.53至-0.08），p<0.001]。相比之下，这表明CVR和CBF降低的负面影响显著超过血压和动脉僵硬度的影响，从而主要塑造了整体模型。与对照组相比，仅在大脑大动脉疾病参与者（SMD=-2.09 [95%可信区间：-3.57，-0.62]）以及小血管疾病参与者（SMD=-0.85 [95%可信区间-1.34，-0.36]）中观察到CF降低的趋势。我们进一步阐述了潜在机制，并讨论了它们与认知障碍的相互联系。
在一个恶性循环中，淋巴系统、神经血管单元、血脑屏障、自动调节和反应性的功能失调机制发挥着不同的作用，导致大脑大动脉和/或小血管疾病患者的CF降低和认知风险增加。CVR和CBF的降低表明CF降低，这与≥60岁老年人群认知障碍风险增加相关。
