Joseph A Ackah, Xuelong Li, Huixing Zeng, Xiangyan Chen
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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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":"21 1","pages":"12"},"PeriodicalIF":4.7000,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12016073/pdf/","citationCount":"0","resultStr":"{\"title\":\"Imaging-validated correlates and implications of the pathophysiologic mechanisms of ageing-related cerebral large artery and small vessel diseases: a systematic review and meta-analysis.\",\"authors\":\"Joseph A Ackah, Xuelong Li, Huixing Zeng, Xiangyan Chen\",\"doi\":\"10.1186/s12993-025-00274-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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]. 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引用次数: 0
摘要
背景:大脑大动脉和小血管疾病被认为是神经系统疾病的基础。我们探讨了神经血管解耦、血脑屏障功能障碍(BBB)、淋巴通路受损、脑血管反应性(CVR)和自动调节受损的机制,这些机制是如何通过各种神经成像技术识别的,影响大脑大动脉和小血管疾病。方法:回顾1990 ~ 2024年报道的与衰老相关的大脑大动脉和小血管疾病的神经影像学表现。52项研究涉及23,693名参与者探讨了疾病机制,其中9项研究(样本量= 3,729)比较了脑大动脉和小血管疾病参与者(目标组)和无血管疾病对照组之间的脑血管功能指标(CF)。CF的测量包括CVR、脑血流量(CBF)、血压和动脉硬度。结果:9项研究(样本量= 3,729,平均年龄= 60.2±11.5岁)的结果显示CVR [SMD = - 1.86 (95% CI - 2.80, - 0.92)]和CBF [SMD = - 2.26 (95% CI - 4.16, - 0.35)]的负效应大小分别表明目标组与对照组相比脑血管功能降低。相反,血压[SMD = 0.32 (95% CI 0.18, 0.46)]和动脉硬度[SMD = 0.87 (95% CI 0.77, 0.98)]的测量值显著升高,这表明目标组脑血管功能较差。在联合模型中,总体平均效应大小为负[SMD = - 0.81 (95% CI - 1.53至- 0.08)],p结论:在恶性循环中,淋巴系统、神经血管单元、血脑屏障、自动调节和反应性中的功能失调机制在脑大动脉和/或小血管疾病患者中降低CF和认知风险方面发挥着不同的作用。CVR和CBF的减少表明CF的减少,这与60岁以上的老年人认知障碍风险增加有关。
Imaging-validated correlates and implications of the pathophysiologic mechanisms of ageing-related cerebral large artery and small vessel diseases: a systematic review and meta-analysis.
Background: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
期刊介绍:
A well-established journal in the field of behavioral and cognitive neuroscience, Behavioral and Brain Functions welcomes manuscripts which provide insight into the neurobiological mechanisms underlying behavior and brain function, or dysfunction. The journal gives priority to manuscripts that combine both neurobiology and behavior in a non-clinical manner.