The enigma of cerebral blood flow and cognition

Abstract

The relationship between cerebral blood flow (CBF) and cognitive function has been widely explored, although the extent to which CBF influences cognition remains inconclusive. Using a placebo-controlled, randomized cross-over design, Shoemaker et al. (2020) assessed cerebrovascular function, cerebral autoregulation and cognitive performance before and following a dose of indomethacin (a potent cerebral vasoconstrictor, thereby aiming to acutely reduce cerebral perfusion) in 25 healthy young and older adults (aged 18–35 years and 50–75 years, respectively). The results of their study illustrate a considerable reduction in CBF (∼31%) and only a slight reduction in cognitive performance (∼7%) post-indomethacin, which was not correlated with the reduction in CBF. These findings were consistent within both age groups. The novel findings reported by Shoemaker et al. (2020), demonstrate the profound resiliency of cognitive performance regardless of acute reductions in cerebral perfusion, importantly, in both young and older adults (Shoemaker et al. 2020). Below, we discuss the possible reasons for this cognitive resiliency, in addition to providing future directions for research in the realm of cerebral perfusion and cognition. The findings reported by Shoemaker et al. (2020) highlight the brain’s buffering capacity and the ability to maintain cognitive function irrespective of acute reductions in CBF by ∼30%. Perhaps this is not surprising given that the brain is able to significantly increase its oxygen extraction fraction in the face of reduced CBF to maintain a constant cerebral metabolic rate of oxygen. For example, in syncope prone older adults, McHenry et al. (1961) demonstrated that cerebral oxygen extraction increased from ∼43% at rest to 77% before presyncope, with a reduction in CBF by ∼50%. Given the recent findings reported by Shoemaker et al. (2020) where a 30% reduction in CBF did not elicit noticeable changes in cognition (at least related to CBF), it could be suggested that the healthy brain is able to compensate for acute and transient decreases in blood flow beyond a 30% reduction without any observable functional deficits in brain/cognitive function. It is unreasonable to suggest that oxygen can be extracted up to the critical value of ∼70% (as observed by McHenry et al. 1961) without cognitive deficit because neural function is probably affected prior to reachingmaximal extraction. Accompanying reductions in perfusion are increases in CO2, hydrogen and temperature, all of which may independently affect cognition despite increases in cerebral oxygen extraction. A challenging but insightful study in the future might attempt to reveal the upper limits of the brains capacity to respond to altered haemodynamic environments (i.e. reductions in CBF) and sustain cognitive function. Before doing so, however, the enigma that is cognition must be explored,