Fulop Gabor A, Tarantini Stefano, Yabluchanskiy Andriy, Molnar Andrea, Prodan Calin I, Kiss Tamas, Csipo Tamas, Lipecz Agnes, Balasubramanian Priya, Farkas Eszter, Toth Peter, Sorond Farzaneh, Csiszar Anna, Ungvari Zoltan
Vascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma.
Translational Geroscience Laboratory, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma.
Am J Physiol Heart Circ Physiol. 2019 May 1;316(5):H1124-H1140. doi: 10.1152/ajpheart.00776.2018. Epub 2019 Mar 8.
There has been an increasing appreciation of the role of vascular contributions to cognitive impairment and dementia (VCID) associated with old age. Strong preclinical and translational evidence links age-related dysfunction and structural alterations of the cerebral arteries, arterioles, and capillaries to the pathogenesis of many types of dementia in the elderly, including Alzheimer's disease. The low-pressure, low-velocity, and large-volume venous circulation of the brain also plays critical roles in the maintenance of homeostasis in the central nervous system. Despite its physiological importance, the role of age-related alterations of the brain venous circulation in the pathogenesis of vascular cognitive impairment and dementia is much less understood. This overview discusses the role of cerebral veins in the pathogenesis of VCID. Pathophysiological consequences of age-related dysregulation of the cerebral venous circulation are explored, including blood-brain barrier disruption, neuroinflammation, exacerbation of neurodegeneration, development of cerebral microhemorrhages of venous origin, altered production of cerebrospinal fluid, impaired function of the glymphatics system, dysregulation of cerebral blood flow, and ischemic neuronal dysfunction and damage. Understanding the age-related functional and phenotypic alterations of the cerebral venous circulation is critical for developing new preventive, diagnostic, and therapeutic approaches to preserve brain health in older individuals.
人们越来越认识到血管因素在与老年相关的认知障碍和痴呆（VCID）中的作用。强有力的临床前和转化证据将脑动脉、小动脉和毛细血管与年龄相关的功能障碍和结构改变与老年人多种类型痴呆的发病机制联系起来，包括阿尔茨海默病。脑的低压、低速和大容量静脉循环在维持中枢神经系统内环境稳定方面也起着关键作用。尽管其具有生理重要性，但脑静脉循环与年龄相关的改变在血管性认知障碍和痴呆发病机制中的作用却鲜为人知。本综述讨论了脑静脉在VCID发病机制中的作用。探讨了脑静脉循环与年龄相关的失调的病理生理后果，包括血脑屏障破坏、神经炎症、神经退行性变加剧、静脉源性脑微出血的发生、脑脊液生成改变、类淋巴系统功能受损、脑血流调节异常以及缺血性神经元功能障碍和损伤。了解脑静脉循环与年龄相关的功能和表型改变对于开发新的预防、诊断和治疗方法以保护老年人的脑健康至关重要。
