High-intensity interval exercise and cerebrovascular health: curiosity, cause, and consequence

Abstract

Exercise is a uniquely effective and pluripotent medicine against several noncommunicable diseases of westernised lifestyles, including protection against neurodegenerative disorders. High-intensity interval exercise training (HIT) is emerging as an effective alternative to current health-related exercise guidelines. Compared with traditional moderate-intensity continuous exercise training, HIT confers equivalent if not indeed superior metabolic, cardiac, and systemic vascular adaptation. Consequently, HIT is being promoted as a more time-efficient and practical approach to optimize health thereby reducing the burden of disease associated with physical inactivity. However, no studies to date have examined the impact of HIT on the cerebrovasculature and corresponding implications for cognitive function. This review critiques the implications of HIT for cerebrovascular function, with a focus on the mechanisms and translational impact for patient health and well-being. It also introduces similarly novel interventions currently under investigation as alternative means of accelerating exercise-induced cerebrovascular adaptation. We highlight a need for studies of the mechanisms and thereby also the optimal dose-response strategies to guide exercise prescription, and for studies to explore alternative approaches to optimize exercise outcomes in brain-related health and disease prevention. From a clinical perspective, interventions that selectively target the aging brain have the potential to prevent stroke and associated neurovascular diseases.

Figure 1

Schematic summarizing proposed mechanisms by which exercise training may alter brain structure and function as well as lower the risk of brain-related dysfunction and disease via alterations in systemic function. BDNF, brain-derived neurotrophic factor; CBF, cerebral blood flow; CO₂, carbon dioxide; eNOS, endothelial nitric oxide synthase; IGF-1, insulin-like growth factor 1; MAP, mean arterial blood pressure; NO, nitric oxide; PGC-1α, peroxisome proliferator-activated receptor-γ coactivator; ROS, reactive oxygen species; RNS, reactive nitrogen species; VEGF, vascular endothelial growth factor.

Figure 2

Top panel: Schematic comparing high-intensity interval exercise training (HIT) against traditional exercise guidelines recommended by leading health agencies (e.g., World Health Organization and American College of Sports Medicine). The HIT protocol illustrated here consists of 6 × 30-second all-out cycling efforts separated by 4.5 minutes of active recovery at very low intensity (e.g., 30 W). This HIT protocol is typically performed three times per week, while exercise training under the traditional model consists of continuous moderate intensity cycling at 65% of maximal aerobic power (V̇O₂max) for 60 minutes, five times per week. Weekly training volume is ~90% lower and time commitment ~one-third for HIT versus that of traditional aerobic exercise training. Bottom panel: Schematic comparing a ‘clinical HIT' protocol against traditional exercise guidelines. This HIT protocol consists of 4-minute intervals of exercise at 85% to 95% of heart rate maximum, separated by 3-minute low-intensity active recovery. A recent meta-analysis of studies utilizing this clinical model of HIT in patients with lifestyle-induced chronic cardiometabolic disease revealed that HIT induced greater reductions in blood pressure, improved blood glucose control, and increased aerobic capacity to a greater extent than did exercise conducted according to traditional guidelines; furthermore, no increase in adverse events was reported with HIT.

Figure 3

The pros and cons of BRAIN-HIT. BBB; brain–blood barrier; BDNF, brain-derived neurotrophic factor; CBF, cerebral blood flow; HIT, high-intensity interval exercise training; MICT, moderate intensity continuous exercise training; VA, vertebral arteries; VV̇O₂ max, maximal aerobic power.

Figure 4

This figure illustrates the potential pathways through which the components of physical activity (intensity, duration, mode, and frequency) as well as other conditioning strategies may lead to beneficial adaptation of brain structure and function. Note that the interventions/stimuli can be applied individually or in combination, and the induced physiologic strain and integration of humoral, metabolic, and molecular signalling, sensoring and transcription may be modulated by individual characteristics (age, sex, and clinical status) and/or other factors (e.g., nutritional supplements) to influence the nature of brain structure and function adaptation. AMPK, AMP-activated protein kinase; BDNF, brain-derived neurotrophic factor; CRP, C-reactive protein; eNOS, endothelial nitric oxide synthase; IGF-1, insulin-like growth factor 1; IL-6, Interleukin 6; LTP, Long-term potentiation; NFkβ, nuclear factor kappa B; NO, nitric oxide; PGC-1α, Peroxisome proliferator-activated receptor-γ coactivator; RNS, reactive nitrogen species; ROS, reactive oxygen species; SIRT 1, Sirtuin 1; VEGF, vascular endothelial growth factor.