Point/counterpoint: Arterial blood pressure response to exercise does relate to exercise-induced improvement in cognitive function

Abstract

Exercise is a beneficial intervention to prevent cognitive dysfunction. However, an optimal exercise prescription for preventing dementia has not been established because the physiological mechanism(s) of exercise-induced improvements in cognitive function remains unclear. Interestingly, our recent study demonstrated that individuals with a higher exercise pressor response exhibit less exercise-induced cognitive improvement, suggesting that individual differences in cardiovascular responses to exercise or its associated physiological factors, may be related to exercise-induced alterations in cognitive function. Therefore, consideration of individual cardiovascular responses is warranted to develop appropriate exercise prescriptions for a given individual to prevent cognitive dysfunction.

The number of patients with dementia is increasing yearly as the older population grows. Thus far, however, there is no optimal medical treatment (e.g., drugs) to prevent or cure dementia. Epidemiological studies have reported that the risk of developing dementia with aging is lower in physically active individuals compared to sedentary people, ¹ indicating that regular exercise is an important intervention for preventing the onset of dementia. Furthermore, our recent study confirmed that acute bouts of even small muscle exercise, such as interval handgrip exercise transiently improve cognitive function (i.e., executive function) in healthy young indivisuals. ² It is speculated that the exercise-induced improvement in cognitive function is related to the stimulation of the brain through several underlying factors (e.g., cerebral blood flow, neural activity) during exercise, however, the physiological mechanism of exercise-induced improvement in cognitive function remains unclear.

The relationship between exercise and cognitive function also remains partially unclear because there are substantial differences between studies in dose-effect, types of exercise, exercise duration, and cognitive outcomes. In addition, the effect of acute exercise, despite in same type of exercise, duration and intensity, on improving cognitive function varies greatly among even healthy individuals. ³ It is suggested that establishing the optimal personalized exercise prescription is needed to maintain normal cognitive function or prevent cognitive decline (i.e., dementia). Therefore, understanding the physiological mechanism between-individual differences in the effect of exercise on cognitive function may be useful for establishing a personalized exercise prescription. Acute bouts of exercise-induced physiological changes resulted in a long-term modulation in various factors (e.g., cerebral neural activity, neurotrophic factor, and neuroendocrine), which is related to acute exercise-induced cognitive improvement following exercise, has been reported. ⁴ Under this research background, we speculated that the individual differences in these physiological changes during exercise might be related to individual differences in exercise-induced improvement in cognitive function. Indeed, we recently obtained the result that healthy young individuals with a higher blood pressure response to acute interval handgrip exercise have less exercise-induced cognitive improvement (executive function). ² In other studies, it has been reported that acute exercise-induced improvements in cognitive function are greater in women,^3,5 who have typically smaller blood pressure responses to exercise relative to men. ⁶ It may be argued that the greater benefit from exercise in women is partly attributed to differences in exercise pressor response, supporting our speculation of the relationship between changes in cognitive function and exercise pressor response to exercise.

These previous studies^2,3,5 do not directly show a cause-and-effect relationship between cognitive improvement and exercise pressor response at this time because systemic hemodynamic changes during exercise are definitely not the sole mechanism, and blood pressure regulates some physiological factors that influence cognitive function; ⁴ however, several possibilities may be considered. First, as speculated in our previous paper, ² an individual difference in exercise pressor response indirectly may reflect the exercise-induced change in brain catecholamine concentration associated with arousal level, which affects exercise-induced improvement in cognitive function. ⁴ In support of our argument, it is well known that higher arousal levels more than necessary attenuated cognitive function with neural noise. ⁴ Second, exaggerated exercise pressor response is attributed to endothelium dysfunction, ⁶ which may disturb the benefit from exercise based on robust literature regarding endothelium dysfunction in relation to dementia and mild cognitive impairment. ⁷ Third, the individual difference in exercise pressor response may affect the cerebral blood flow response to exercise which is a candidate mechanism for exercise-induced cognitive improvement. ⁸ In support of our argument, the cerebral blood flow response to exercise was lower in normotensive young adults who have exaggerated exercise pressor response than in controls. ⁹ However, these explanations are still speculative; thus, further investigations are necessary to establish evidence for this relationship. For instance, we need to investigate whether the exercise-induced cognitive improvement is different between groups who have a different level of exercise pressor response (e.g., sex difference or cardiovascular diseases such as hypertension), and furthermore this benefit from exercise related to change in arousal levels (e.g., locus coeruleus-norepinephrine system), flow-mediated dilation (i.e., endothelium function) or cerebral blood flow response. In addition, it is unclear whether this relationship can be generalized to different exercise modalities, cognitive function domains, and groups (e.g., older individuals, and patients with Dementia or Alzheimer’s disease). However, we believe that these findings provide the possibility that cardiovascular response to exercise or its associated physiological alterations may be related to exercise-induced improvement in cognitive function.

In clinical studies, decreases in resting blood pressure with antihypertensive drug use in patients with arterial hypertension increase the risk of developing brain disease and dementia, which may be associated with antihypertensive drug-induced decreases in cerebral perfusion pressure and consequently total cerebral blood flow. ¹⁰ This clinical finding may support that cognitive function is affected by the regulation of arterial blood pressure and systemic circulation, as well as its related cerebral blood flow during exercise.

With this background in mind, the individual differences in the effect of exercise on improving cognitive function may be closely related to the systemic circulatory response to exercise (exercise pressor response) or its associated physiological alterations (e.g., endothelial function ⁶ ). The devolvement of academic questions about what causes inter-individual differences in cognitive function for exercise (including aging, circulatory system diseases, physical fitness, sex differences, and race) may be important to develop adequate exercise prescriptions for a given individual to prevent cognitive dysfunction.