Aortic Stiffness and Cerebral Blood Flow

As the world population ages, various conditions of aging, including mild cognitive impairment and dementia, are becoming increasingly prevalent and demand our immediate attention in order to curtail a looming epidemic. Cognitive impairment is frequently dichotomized into vascular or Alzheimer types, although standard vascular disease risk factors are key risk factors at both ends of what is clearly a spectrum of cognitive disorders. Overlap of vascular and cognitive risk factors is partially attributable to atherosclerosis and clinically apparent macrovascular strokes. In addition, growing evidence suggests that microvascular dysfunction and damage may play an insidious, substantial role in the overall burden of cognitive diseases.1 Increased aortic stiffness is associated with microvascular dysfunction, which may contribute to cognitive impairment and overlap between vascular and cognitive risk factors. Fuel reserves in the brain are limited, resulting in obligatory tight coupling between blood flow and demand.2 Increased brain activity is associated with a prompt increase in regional blood flow know as functional hyperemia. In addition, global brain blood flow is maintained relatively constant across a wide range of pressures through the process of autoregulation, wherein cerebrovascular resistance changes in proportion to perfusion pressure, leaving flow unchanged. Autoregulation preserves flow during hypotension and protects against microvascular barotrauma during hypertension. Functional hyperemia and autoregulation are critically dependent on intact resistance vessel reactivity. Increased aortic stiffness is associated with impaired microvascular reactivity and a blunted hyperemic response to ischemia.3 Aortic stiffening also predisposes to blood pressure lability, creating a setup for transient episodes of hypotensive ischemia and hypertensive barotrauma. Consistent with these observations, aortic stiffness is associated with signs of microvascular brain injury, including white matter hyperintensities and subcortical infarctions detected by magnetic resonance images of the brain,4 suggesting that aortic stiffening may be associated with microvascular dysfunction and damage in the brain. In the current issue of American Journal of Hypertension, Tarumi et al. tested the hypothesis that aortic stiffening is associated with abnormal resting brain blood flow by evaluating relations between regional brain blood flow, measured by magnetic resonance imaging arterial spin labeling, and aortic stiffness, assessed as carotid-femoral pulse wave velocity, in a sample of 37 community dwelling adults with no history of overt cardiovascular or neurologic disease.5 The authors found that higher carotid-femoral pulse wave velocity was associated with lower flow in frontal and parietal white matter; relations in frontal white matter persisted following adjustment for several potential confounders. By documenting reduced blood flow in a region of the brain predisposed to microvascular damage in individuals with abnormal aortic stiffness, this study provides an important step forward in our understanding of potential mechanisms contributing to target organ damage in the presence of increased carotid-femoral pulse wave velocity. The study raises questions that will need to be addressed in future studies. The sample size was small so adjustment for additional potential confounders, such as diabetes and lipid abnormalities, was not possible. Several comparisons were evaluated without adjustment for multiple testing and there was a suggestion of heterogeneity across brain regions. A larger sample will be required to establish if heterogeneity exists and observed deficits in one or more regions survive adjustment for multiple testing. If regional heterogeneity of the carotid-femoral pulse wave velocity effect is real, additional work to sort out potential mechanisms would be informative. A larger study of similar design that additionally evaluates flow reactivity and relations between microvascular abnormalities and cognitive function would address many of these questions, extend the present observations and move us a step closer to closing the loop between potentially modifiable vascular risk factors and cognitive function. G.F.M. is owner of Cardiovascular Engineering, Inc., a company that designs and manufactures devices that measure vascular stiffness. The company uses these devices in studies that evaluate the effects of diseases and interventions on vascular stiffness.