High intensity interval training (HIIT) help prevent age-related cognitive illnesses


High intensity interval training (HIIT) may be doing more than just keeping you fit and strong—it may also help prevent age-related cognitive illnesses, such as dementia.

A University of Queensland study found high intensity interval exercise may be more effective than continuous exercise in increasing brain blood flow in older adults.

Researcher Dr. Tom Bailey from the Centre for Research on Exercise, Physical Activity and Health at UQ’s School of Human Movement and Nutrition Sciences said that while high intensity interval training was popular for improving cardiovascular health, its effect on brain health and function wasn’t known.

“As we age, the flow of blood to the brain and arterial function decreases,” Dr. Bailey said.

“These factors have been linked to a risk of cognitive decline and cardiovascular events, such as stroke.

“Finding ways to increase brain blood flow and function in older adults is vital.”

The study, conducted in collaboration with Associate Professor Christopher Askew at the University of the Sunshine Coast and neuroscientists at the German Sport University Cologne, was the first of its kind to compare the brain blood flow in younger and older men during both continuous and interval exercise.

Interval exercise is characterized by short bouts of intense activity separated by rest periods.

“One of the key takeaways from the study was that both the exercise and the rest period were important for increasing brain blood flow in older adults,” Dr. Bailey said.

“This study shows that interval-based exercise was as effective as continuous exercise for increasing brain blood flow in older adults during the periods of activity, and more effective than continuous exercise when we measured the overall blood flow increases during both the exercise and the rest periods.

“The benefits of exercise on brain function are thought to be caused by the increase in blood flow and shear stress, the frictional force of blood along the lining of the arteries, which occurs during exercise.

“This study aimed to identify the type or format of exercise that causes the greatest increases in brain blood flow, so we could help to optimize exercise programs to enhance brain function.”

While this study focused on short-term increases in brain blood flow, Dr. Bailey said the next step was to investigate the benefits of interval exercise on brain health in the long term.

The research is published in Medicine & Science in Sports & Exercise.

Strenuous physical activity (e.g., exercise) is the most accessible, effective, pluripotent, and safe intervention to improve and maintain health, as well as treat most modern chronic diseases.123,4 

Evidence from randomized controlled trials indicates that exercise is as effective as drug interventions in terms of mortality benefits in the secondary prevention of coronary heart disease, treatment of heart failure and prevention of diabetes, and is more beneficial than drug treatment in stroke rehabilitation.5 

Thus, exercise has a significant role to play in both the prevention and treatment of disease.

However, despite its clear benefits, more than one-third of the global adult population, and four-fifths of adolescents, fail to meet current public health guidelines for physical activity67 (i.e., ⩾30 minutes of moderate-intensity exercise on at least 5 days of the week (⩾150 min/week), or 20 minutes of vigorous-intensity aerobic exercise training on at least 3 days of the week (⩾75 min/week)).89 

Inactivity appears more prevalent in higher income countries (e.g., 80% of British and 90% of American adults1011), particularly among the less wealthy, who also comprise the majority of these populations.1213

 Global health statistics highlight ‘physical inactivity’ as a top 10 risk factor for poor health,14 associated with an increased risk of premature cardiovascular and cerebrovascular mortality.15161718 

Therefore, to better harness its health benefits, we need to more effectively establish the underlying mechanisms, and therefore the role of each exercise parameter (intensity, frequency, mode, and duration) in optimizing health and well-being.

This knowledge will inform exercise prescription guidelines and allow exploration of alternative approaches to access the health benefits that exercise provides for both healthy and diseased populations.

The benefits of exercise for the brain are becoming increasingly evident but remain poorly understood.

Regular exercise promotes angiogenesis, neurogenesis, and synaptic plasticity,1920,21 which translate into improved and more efficient cerebral perfusion and metabolism.2223

Such neural and vascular adaptations contribute to the maintenance of cognitive function, which declines during aging and more markedly in dementia.3242526 

However, the mechanisms that underpin the neuroprotective benefits of exercise remain to be established, and thus so does the rationalization of exercise parameters.

Optimizing exercise to target the aging brain has the potential to prevent stroke and associated neurovascular diseases including dementia, thus reducing the global economic burden associated with the aging population.

This is critical given that the societal cost of dementia was estimated at >$600 billion globally in 2010, and in the United Kingdom the cost of dementia alone almost matched the combined costs of cancer, heart disease, and stroke.27 

Urgent implementation of effective countermeasures is critical to fully prepare for the challenges of the world’s changing demographics and to create an equitable, affordable, and sustainable aging society for the future. Since there are no curative treatments currently available, major efforts need to focus on prevention, with emphasis on modifiable risk factors such as engagement in physical activity.Go to:

Conceptual Focus

In this review, we critically address to what extent high-intensity interval exercise training (HIT) may improve cerebrovascular function, with a focus on the mechanisms and translational impact for patient health and well-being.

We begin by highlighting the potential mechanisms by which exercise can improve brain function.

Next, we review evidence to illustrate the effectiveness of HIT in healthy and clinical populations associated with impaired brain function. We then discuss the potential danger that HIT may pose to the brain, and how current understanding of cerebral blood flow (CBF) regulation could be used to limit potential risk and inform novel conditioning approaches that target the brain.

Finally, we introduce novel interventions that are under investigation as alternative means of accelerating exercise-induced cerebrovascular adaptation, and suggest avenues for future research.

Exercise and the functional regulation of cerebral blood flow

The regulation of CBF involves complex interactions between brain metabolic and neuronal activity, blood pressure, partial pressure of arterial carbon dioxide (PaCO2), cardiac output, and, perhaps sympathetic nervous system activity28 (see review by Ogoh and Ainslie29). Exercise affects all of these factors and their interactions.29

 Traditionally, CBF during exercise was thought to be unchanged from rest;3031 however, more recent studies utilizing technologies with greater temporal resolution (e.g., transcranial Doppler and magnetic resonance imaging) have showed that global CBF increases with exercise intensity up to ~70% of maximal aerobic power (i.e., V̇O2max),32333435 although region-specific increases only to brain areas associated with locomotion have also been suggested.3637

 This elevation in CBF is mediated via elevations in cerebral metabolic and neuronal activity,3839 blood-borne molecular factors (e.g., nitric oxide (NO), vascular endothelial growth factor (VEGF)) and PaCO2;404142 the latter two likely to have a global effect.

Increased blood flow elevates mechanical shear stress within blood vessels, which has a beneficial effect on the endothelium via Akt- (protein kinase B) dependent expression of endothelial nitric oxide synthase, NO generation, and complementary improvement of antioxidant defences (reviewed in Bolduc et al37).

The increase in vascular NO bioavailability is considered as a key factor in the maintenance of cerebrovascular function and optimal regulation of CBF.

While in humans much of this premise has been inferred from studying shear stress-mediated improvement in endothelial function of the systemic vasculature (e.g., via flow-mediated dilation of the brachial artery),43 extrapolating this to the cerebrovasculature seems reasonable, although with some caveats specific to high-intensity exercise as will be discussed below.

Evidence from animal-based and cell-culture studies provides strong support for shear stress-mediated adaptation of the cerebrovasculature (see review by Bolduc et al37). Further, Padilla et al44 have proposed that alternative signals (i.e., circumferential stretch (cyclic strain), circulating humoral factors) to chronic exercise may act independently or synergistically with shear forces in the modulation of systemic endothelial adaptations in noncontracting tissues (e.g., the cerebrovasculature). Nevertheless, the role of different exercise parameters—and thus blood flow rate/profile—on cerebrovascular endothelium has not been studied. In the systemic vasculature of humans, however, an exercise intensity-dependent response is evident acutely;45severe HIT46 as well as moderate-intensity continuous exercise training (MICT)47 can improve flow-mediated dilation, and MICT increases arterial compliance whereas resistance exercise reduces it.4748 Whether such effects translate to the cerebrovasculature is, however, complicated by other effects of intense exercise (see below).

Another key component of exercise is the increased neural activation associated with generating movement. While elevated neuronal activity will increase perfusion to meet metabolic demand (i.e., neurovascular coupling)49 and thus have an influence in shear stress-mediated adaptation, exercise also activates the expression of genes associated with neuroplasticity and stimulates neurogenesis.5051 

These processes may thus represent a primordial constituent in the positive relationship between exercise and brain health.

Different exercise parameters may influence the rate and magnitude of the neural activation, which in turn may alter the vascular response and potentially the signalling stimulus for adaptation (vascular and neural).

Understanding the cellular and molecular basis of exercise-induced neuroprotection is vital for optimizing exercise to improve brain health.

Research to date has revealed several key exercise-induced mediators of neurogenesis, synaptic plasticity, and brain angiogenesis (e.g., brain-derived neurotrophic factor (BDNF), VEGF, insulin-like growth factor 1 (IGF-1)), along with their gene-level and humoral modulators (e.g., tropomyosin receptor kinase B, protein kinase C, GluR5, synapsin I, fibronectin type III domain containing 5, irisin; for recent reviews, see Voss et al.51and Phillips et al.52). 

Figure 1 illustrates such proposed local and humoral mediators of exercise-induced adaptation of brain structure and function. Much of the evidence for these cellular and molecular pathways necessarily comes from animal work, thus translation to the human remains speculative. Nevertheless, the role of exercise intensity has received very little attention even in these models, let alone in humans.

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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.

Exercise perturbs redox homeostasis transiently within cells and tissues. While exercise-induced formation of free radicals and reactive oxygen (ROS) and nitrogen (RNS) species was originally suggested to cause structural tissue damage, recent evidence has shown that in physiologically controlled, albeit undefined concentrations, they serve as critical signalling molecules that mediate adaptation.53, 54

Radical species upregulate antioxidant enzymes55 and increase neurotropic factors, such as BDNF, VEGF, and IGF-1.56, 57

The Janus Face of exercise-induced oxidative-nitrosative-inflammatory stress reflects a fundamental concept known as hormesis:58 a toxicological term characterizing a biphasic dose-response encompassing a low-dose stimulation or beneficial effect and a high-dose inhibitory or toxic effect;59 thus quantifying the impact of each exercise parameter on radical species may be a crucial step in determining the best exercise strategy for optimizing brain structure and function.

Accordingly, people with higher baseline oxidative-nitrosative-inflammatory stress (e.g., older or diseased) might benefit from a different prescription of exercise with respect to this mediator of (mal)adaptation.

While this review is focused on the effects of exercise on the brain, an important point to be made is that exercise confers systemic metabolic and immunomodulatory benefits. Indeed, hyperglycemia and diabetes are important risk factors for dementia,60 and systemic low-grade chronic inflammation is evident in populations with mild cognitive impairment and Alzheimer’s disease.61

Numerous exercise training studies, including those using models of HIT (discussed next), have shown the efficacy of exercise as a tool to lower blood glucose levels, improve insulin sensitivity, and overall glycemic control, as well as reduce neuro-inflammation (see Figure 1).
High-Intensity Interval Exercise Training; An Emerging Paradigm
There is a burgeoning interest in HIT as an alternative means of improving health, motivated in part by the need to combat the perceived and frequently reported ‘lack of time’ barrier associated with traditional exercise guidelines, which promote MICT.62, 63 There are various forms of HIT,64, 65 but it generally involves repeated bouts of relatively brief intermittent exercise, often performed at an intensity close to (~85% to 95%) or beyond maximal aerobic power.66, 67 Two examples of the HIT profile are illustrated in Figure 2.

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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 Organization8 and American College of Sports Medicine9). 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.69 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.77

Compared with traditional MICT, emerging evidence indicates that HIT provides equivalent if not indeed superior metabolic, cardiac, and systemic vascular adaptations, thereby supporting more time-efficient approaches to optimize metabolic and cardiovascular health (e.g.;646869,7071727374757677 see Figure 3).

Such studies have provided mechanistic support for the epidemiologic observations that intensity of exercise appears more important than its duration in preventing cardiovascular disease.7879 

High-intensity interval exercise training has also been shown to be more effective than traditional exercise interventions for cardiac function in various diseases for which there was major concern regarding its safety and appropriateness.6472 

The evidence to date in the cardiac rehabilitation setting indicates a low risk for acute adverse cardiovascular events during HIT, albeit perhaps ~5 times higher than that observed during MICT (1 event per 23 182 hours of HIT exercise versus 1 event per 129 456 hours of MICT80).

Further, a recent meta-analysis of HIT studies in patients with lifestyle-induced chronic cardiometabolic disease (coronary artery disease, heart failure, hypertension, metabolic syndrome, and obesity) reported no adverse events related to the exercise training, and revealed that HIT provided almost twice the improvement in cardiorespiratory fitness (i.e., V̇O2max) – a strong predictor of mortality17 – compared with MICT (19.4% versus 10.3% increase in maximal rate of oxygen consumption; i.e., V̇O2max).77

 Further, one study in hypertensive patients included within this meta-analysis reported that 12 weeks of HIT lowered blood pressure by more than twice that achieved with MICT (ambulatory 24-hour systolic blood pressure down 12 versus 4.5 mm Hg, and diastolic blood pressure down 8 versus 3.5 mm Hg).

This study is noteworthy as hypertension is the single most important risk factor for stroke. However, before exercise guidelines are rewritten to make shorter bouts of higher intensity exercise a more convenient and arguably more effective option for healthy and diseased populations to consider, what are the corresponding implications for brain health?

Research on the impact and potential benefits of HIT on the cerebrovasculature and corresponding implications for cognitive function is notably absent (e.g., no studies have examined even just the effects of HIT on CBF), which is surprising given the importance of brain structure and function in health and disease.

Moreover, HIT may present ‘unique’ dangers for the brain in the short term that warrant clinical consideration.

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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.

More information: Timo Klein et al. Cerebral Blood Flow during Interval and Continuous Exercise in Young and Old Men, Medicine & Science in Sports & Exercise (2019). DOI: 10.1249/MSS.0000000000001924

Journal information: Medicine & Science in Sports & Exercise
Provided by University of Queensland


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