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 reaching maximal 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, as well as the abundance of factors that can alter it, alongside CBF. Indomethacin undoubtedly has a significant impact on cerebral hemodynamics; however, it is important to clarify the meaning of cognition to correlate an alteration in CBF and changes in cognitive function. Cognition refers to the mental process of acquiring knowledge and understanding thoughts. Cognition encompasses several aspects such as attention, perception, judgment, memory, language, problem-solving, decision making, reasoning and mental switching (i.e. cognition flexibility). Several factors that can impact cognition need to be considered in experimental studies that assess cognition. The correlation between cerebral blood flow alterations and cognitive performance remains unclear; accordingly, to indicate a strong correlation between the two variables, multiple factors should be controlled. The Montreal Cognitive Assessment is an ideal screening tool to rule out long-term cognitive impairment during the recruitment of participants. However, before each experimental visit, other factors, such as glucose level, sleep history and mood disorders, should be considered because of their potential to cause fluctuations in cognition on a daily basis. Reactive (postprandial) or fasting hypoglycaemia can affect cognition in all ages and is especially apparent in older adults. Therefore, monitoring the blood glucose level during experimental visits in research studies that are implemented to test cognition is advisable. An important consideration, however is the possibility that insulin resistance, if present, can modify the effect of any known glucose concentration. Additionally, the link between sleep deprivation and mood disorders on cognition has been well established. Specifically, one night of no sleep (i.e. sleep deprivation) can cause a deterioration in executive functioning (Skurvydas et al. 2020). There is no universally accepted tool to assess cognition. Several computerized batteries have been used to screen for cognitive impairment, although it is debatable if these batteries are preferred over the traditional paper-based methods. An ideal cognition assessment tool should be brief and have a high negative predictive value. A test that assesses multiple aspects of cognition (e.g. attention, short-term memory, judgment, cognition flexibility, etc.) is preferred. Another factor to consider is mental fatigue; mental fatigue caused by a complex cognition assessment tool can alter measurements. The ideal implementation comprises an assessment strategy that is brief, has a high negative predictive value, assesses multiple cognition aspects and does not contribute to mental fatigue. In addition, repeated exposure to the assessment tool (i.e. practising) before conducting an experiment could improve the participants’ executive functions, which in return can affect the accuracy of cognitive performance. Accordingly, test–retest reliability should be taken into consideration. Along with visuomotor reaction time and inhibition, one key cognitive domain that the Pro, Anti, Pro/Anti task evaluates is mental switching. Mental switching varies during the lifespan of an individual; therefore, comparing mental switching between younger and older adults can be complicated. Importantly, there are two factors to consider, namely fluid intelligence and coping methods, both learned with ageing. As such, relying on mental switching to assess cognition is less than optimal. However, a combination of the Mini-Mental Status Exam, Wisconsin Card Sorting test and Attention and Digit Span can be used during each experimental visit to assess the effect of cerebral blood flow alteration on cognition. These tests are self-administered, relatively quick, have minimal practice effects and assess several domains of cognition (short-term memory, visuospatial/executive, naming, attention, language, abstraction, delayed recall and orientation), making them an appropriate means to assess cognition. Given the discussions above, a putative experimental approach is provided in Fig. 1. The results reported by Shoemaker et al. (2020) may be extended in several directions. First, older adults use neural compensation mechanisms by recruiting a set of brain areas to cope with the increasing attention load required to perform complex tasks (Ansado et al. 2013). How these neural compensation mechanisms are affected by an altered global cerebral blood flow should be considered. Second, future studies should measure neurovascular coupling because this would complement the findings related to cognition. Given that an assessment of cognition selectively increases neural activity, the metabolic activity in the corresponding regions should be elevated (Maggio et al. 2013). Accordingly, increased blood flow as a result of the elevated metabolic activity could be correlated with the participants’ cognitive performance. Third, although the findings reported by Shoemaker et al. (2020) highlight the brain's capacity to cope with acute reductions in cerebral blood flow (probably by increasing the oxygen extraction fraction to maintain metabolic needs), it remains to be determined for how long this lasts. Indeed, over time, the reduced metabolic biproduct washout (reduced venous flow) may impact cognition. Lastly, the enigmatic definition of cognition, as well as the tests that seek to define it, deserves discussion. Indeed, a separate battery of tests to define ‘cognition’ may reveal nuances that might be altered in acute states of reduced cerebral blood flow. No competing interests declared. All authors have approved the final version of the manuscript and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All persons designated as authors qualify for authorship, and all those who qualify for authorship are listed. No funding was received. The authors thank Dr Anthony Bain for his contribution in our journal club discussion.