Department of Psychology, University of Texas, Austin, TX, USA.
J Alzheimers Dis. 2012;32(3):553-67. doi: 10.3233/JAD-2012-120793.
Considerable information is currently available from neuroimaging, pathological, and population-based prospective studies showing that vascular risk factors are independently associated with an increased risk of Alzheimer's disease (AD). Many of these studies indicate that vascular risk factors can predict the clinical development of cognitive dysfunction and AD onset. This review examines the role of cerebral hemodynamics and vasoactive molecules that contribute to the regulation of cerebral perfusion and how three common vascular risk factors to AD, namely, hypertension, diabetes type 2, and atherosclerosis, can alter cerebral blood flow (CBF) regulation and generate perfusion pressure deficits. It is proposed that these vascular risk factors (and presumably other vascular risk factors) initiate chronic brain hypoperfusion that ultimately impair signaling from neurons, astrocytes, and endothelial cells to vascular smooth muscle controlling vessel diameter. Impaired signaling involving vascular pathways in the elderly can attenuate vessel tone and deregulate CBF. Noxious cerebral hemodynamic responses to vascular risk factors and chronic brain hypoperfusion are partly explained by Poiseuille's Law which states that miniscule changes in vessel diameter can have a dramatic effect on vessel resistance and on the rate of blood flow. Using Poiseuille's model, even minor narrowing of arteriolar diameter can lead to major reductions in CBF and in suboptimal delivery of high energy nutrients to the brain, with lethal consequences to brain cells that participate in cognitive function. Regional brain cell loss sets the stage for age-related cognitive impairment and AD onset. Keeping cerebral hemodynamic homeostasis by careful management of vascular risk factors could be a decisive therapeutic target in the prevention of AD.
目前有大量来自神经影像学、病理学和基于人群的前瞻性研究的信息表明，血管危险因素与阿尔茨海默病（AD）的风险增加独立相关。这些研究中的许多表明，血管危险因素可以预测认知功能障碍和 AD 发病的临床发展。本综述探讨了脑血流动力学和血管活性分子在调节脑灌注中的作用，以及 AD 的三种常见血管危险因素，即高血压、2 型糖尿病和动脉粥样硬化，如何改变脑血流（CBF）调节并产生灌注压不足。据推测，这些血管危险因素（以及其他可能的血管危险因素）会引发慢性脑灌注不足，最终损害神经元、星形胶质细胞和内皮细胞向控制血管直径的血管平滑肌发出信号。涉及老年人血管途径的信号受损会减弱血管张力并使 CBF 失调。有害的脑血管对血管危险因素和慢性脑灌注不足的反应部分可以用泊肃叶定律来解释，该定律指出，血管直径的微小变化会对血管阻力和血流速度产生巨大影响。使用泊肃叶模型，即使是微小的动脉直径变窄也会导致 CBF 大幅降低，以及大脑无法获得最佳的高能营养物质供应，从而对参与认知功能的脑细胞造成致命后果。区域性脑细胞丧失为与年龄相关的认知障碍和 AD 发病奠定了基础。通过仔细管理血管危险因素来保持脑血流动力学平衡，可能是预防 AD 的决定性治疗目标。
