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
Abstract 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)...
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2025-04-01
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| Online Access: | https://doi.org/10.1186/s12993-025-00274-1 |
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| author | Joseph A. Ackah Xuelong Li Huixing Zeng Xiangyan Chen |
| author_facet | Joseph A. Ackah Xuelong Li Huixing Zeng Xiangyan Chen |
| author_sort | Joseph A. Ackah |
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| description | Abstract 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. |
| format | Article |
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| language | English |
| publishDate | 2025-04-01 |
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| spelling | doaj-art-39cce74486844171a31ef83ba7a956ce2025-08-20T02:20:05ZengBMCBehavioral and Brain Functions1744-90812025-04-0121112310.1186/s12993-025-00274-1Imaging-validated correlates and implications of the pathophysiologic mechanisms of ageing-related cerebral large artery and small vessel diseases: a systematic review and meta-analysisJoseph A. Ackah0Xuelong Li1Huixing Zeng2Xiangyan Chen3Department of Health Technology and Informatics, The Hong Kong Polytechnic UniversityDepartment of Neurology, The Second Affiliated Hospital, Guangzhou Medical UniversityDepartment of Health Technology and Informatics, The Hong Kong Polytechnic UniversityDivision of Science, Engineering, and Health Studies, College of Professional and Continuing Education, The Hong Kong Polytechnic UniversityAbstract 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.https://doi.org/10.1186/s12993-025-00274-1AgeingNeuroimagingCerebral small vessel diseaseLarge artery diseasePathophysiologyCognitive |
| spellingShingle | Joseph A. Ackah Xuelong Li Huixing Zeng Xiangyan Chen 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 Behavioral and Brain Functions Ageing Neuroimaging Cerebral small vessel disease Large artery disease Pathophysiology Cognitive |
| 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Ageing Neuroimaging Cerebral small vessel disease Large artery disease Pathophysiology Cognitive |
| url | https://doi.org/10.1186/s12993-025-00274-1 |
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