Cerebrovascular adaptations to habitual resistance exercise with aging

Abstract

Resistance training (RT) is associated with improved metabolism, bone density, muscular strength, and lower risk of osteoporosis, sarcopenia, and cardiovascular disease. Although RT imparts many physiological benefits, cerebrovascular adaptations to chronic RT are not well defined. Participation in RT is associated with greater resting peripheral arterial diameters, improved endothelial function, and general cardiovascular health, whereas simultaneously linked to reductions in central arterial compliance. Rapid blood pressure fluctuations during resistance exercise, combined with reduced arterial compliance, could lead to cerebral microvasculature damage and subsequent cerebral hypoperfusion. Reductions in cerebral blood flow (CBF) accompany normal aging, where chronic reductions in CBF are associated with changes in brain structure and function, and increased risk of neurodegeneration. It remains unclear whether reductions in arterial compliance with RT relate to subclinical cerebrovascular pathology, or if such adaptations require interpretation in the context of RT specifically. The purpose of this narrative review is to synthesize literature pertaining to cerebrovascular adaptations to RT at different stages of the life span. This review also aims to identify gaps in the current understanding of the long-term impacts of RT on cerebral hemodynamics and provide a mechanistic rationale for these adaptations as they relate to aging, cerebral vasculature, and overall brain health.

INTRODUCTION

Gradual reductions in cerebral blood flow (CBF) are associated with normal aging in both men and women (1). Age-related reduction in CBF is partially attributed to a reduction in cerebral metabolic rate following progressive neuronal loss (2), and changes in cardiovascular health and function (1, 3). With respect to cardiovascular adaptations, increases in arterial stiffness and reductions in arterial compliance have significant impacts on cerebral blood flow regulation and overall brain health (4, 5). Reductions in vascular compliance are characterized by impaired capacity to buffer high pressures ejected from the heart, which can damage cerebral microvasculature, and subsequently lead to chronic reductions in CBF. Persistent cerebral hypoperfusion is associated with changes in brain structure and function (6–8), as well as heightened risk for neurodegenerative disorders including vascular dementia, Parkinson’s disease, and Alzheimer’s disease (9–11).

Exercise training may serve to mitigate age-related reductions in cerebral perfusion primarily through improvements in overall cardiovascular health (12). The brain is a metabolically demanding organ, requiring precise and stable delivery of blood flow at rest and during physiological stimuli. Exercise challenges CBF regulation as it elicits changes in several physiological determinants of cerebral hemodynamics. To date, a large proportion of literature in the research area of cerebral hemodynamics during exercise has focused on steady-state aerobic exercise (AE) (13–20). Aerobic exercise training (AT) acts as an effective approach to counter age-related declines in CBF and overall brain health. Participation in AT has been associated with improved regional CBF in cortical areas related to the default mode network—an area of the brain affected by both normal aging and Alzheimer’s disease (1, 21). Furthermore, cardiorespiratory fitness levels in older adults are significantly associated with increased gray matter CBF (22). Relative to AT, there is limited literature addressing long-term cerebrovascular adaptations to habitual participation in resistance exercise [i.e., resistance training (RT)].

Resistance exercise (RE) is frequently prescribed to older adults because of its associations with improved metabolism, bone density, muscular strength, and reduced risk for osteoporosis, sarcopenia, and cardiovascular disease (23). Although many of the physiological benefits of RE are well established, the effects of RT on the cerebral vasculature remain unclear and understudied. Generally, participation in RT is associated with positive vascular adaptations [i.e., greater resting brachial arterial diameter (24), improved endothelial function, nitric oxide (NO) production, and general cardiovascular health (25, 26)]. However, in healthy young men, but not young women (27, 28), RT is associated with arterial stiffening and reductions in central arterial compliance (30–35). Interestingly, in middle-aged and older adults who may likely present with age-associated declines in vascular function (36), arterial compliance appears to be unaffected by RT (28, 37–39), and increases in resting CBF have been observed in older adults who regularly partake in RT (40–42). It is unclear why participation in RT appears to increase arterial stiffness in young men but does not elicit similar effects in young women or middle-aged adults (in either men or women).

Given the pathological implications of reduced vascular compliance and increased vascular stiffness, interpreting the impact of RT-induced vascular adaptations on the cerebral vasculature and overall brain health remains a challenge. In consideration of the overall physiological benefits associated with RT, it is unclear whether reductions in arterial compliance and increases in arterial stiffness with RT are markers of subclinical cerebrovascular pathology in the traditional sense. Specifically, these vascular adaptations may require interpretation unique to and within the context of the habitual resistance exerciser. Previous reviews have summarized acute cerebrovascular responses to RE (43) and AE (44); however, a comprehensive account of alterations in cerebral hemodynamic control in resistance-trained individuals does not exist. Therefore, the purpose of this narrative review is to synthesize literature pertaining to cerebrovascular adaptations to RT along different stages of the life course (i.e., cross-sectional comparisons including young, middle-aged, and older adults who habitually participate in resistance exercise or resistance exercise training in previously untrained young and older adults). This review also aims to identify gaps in the current understanding of the long-term implications of RT on cerebral hemodynamics and provide a mechanistic rationale for these adaptations as they relate to aging, cerebrovascular, and overall brain health.

METHODS

Review Scope

This review will cover the following: 1) the relationship between age-related arterial stiffening and its effects on cerebrovascular health, 2) the evidence related to cerebrovascular adaptations to RT in young healthy adults from both training studies and cross-sectional work, 3) acute cerebrovascular responses to RE in untrained older populations, and 4) longer-term cerebral hemodynamic adaptations and alterations in cerebrovascular-related outcomes (i.e., brain structure and brain function) to RT in older adulthood. Although changes in arterial stiffness either with aging or with habitual RT is not the focus of this review, it serves as an important contextual piece for the interpretation of cerebrovascular adaptations to resistance training. The effects of aging and resistance training on arterial stiffness and compliance have been reviewed in depth in several publications (45–49). In the sections reviewing cerebrovascular adaptations and changes in cerebrovascular-related outcomes in response to RT, we also attempt to identify common themes in the adaptations to RT and speculate on mechanisms underlying observed changes in cerebrovascular function.

Following these sections, we will then cover methodological considerations for future RT studies, particularly as they relate to the design of RT programming including key principles of exercise prescription such as exercise type, intensity, duration, tempo, and periodization. The final section of this review will highlight knowledge gaps and provide future directions in the space of cerebrovascular adaptations to RT across the lifespan.

Relationship between Aging, Arterial Stiffness, and Cerebrovascular Health and Function

Aging is associated with increased arterial stiffness and reductions in elastic artery compliance (50). Remodeling of arteries with age can be attributed to several factors, including changes in vessel wall composition (proportion of elastin and collagen fibers) (50), endothelial cell signaling, smooth muscle cell tone (51), and chronic elevations in sympathetic nerve activity (52). Although not the focus of the present review, it is important to acknowledge that age-related arterial stiffening has the potential to impact cerebral vasculature and overall brain health. Specifically, as arterial stiffness increases, the vessel’s ability to dampen high-pressure blood flow ejected from the heart is impaired and may lead to high pulse pressure waves reaching the cerebral microvasculature (53). The cerebral microvasculature is sensitive to high-pressure and pulsatile blood flow (53). As such, microvessels in the cerebral circulation are predisposed to damage when high pressures are not buffered efficiently by conduit arteries. This damage can lead to hypoperfusion or ischemia in neural tissues and subsequent neuronal atrophy or death in brain areas where the supplying vasculature is compromised (54). Cross sectionally, high levels of arterial stiffness are associated with lower gray matter volume, increased white matter hyperintensity load, and impairments in cognitive function (55–57), implicating arterial stiffness as a key mechanism for the progression of negative alterations in brain structure and function. Our previous large population-based study from the United Kingdom Biobank identified that greater indices of arterial stiffness in midlife are associated with lower global gray matter volume and increased white matter hyperintensity load in a 10-yr follow-up, supporting the midlife time period as an opportunity for exercise to mitigate age-associated vascular stiffness in the brain (58).

Arterial stiffening can lead to increased pulsatility of cerebral blood flow (59) and reduced global CBF (5). A study from Tarumi et al. (7) showed that elevations in CBF pulsatility are accelerated with age after midlife and are independently associated with elevations in carotid artery pulse pressure, whereas CBF is linearly decreased with advancing age (7). Reduced cerebral perfusion is associated with deleterious effects on brain structure and function (60), including cerebral tissue atrophy (61) and impaired cognitive function (62). Alterations in brain structure and function are associated with accelerated progression of neurodegenerative conditions such as vascular dementia, Parkinson’s disease, and Alzheimer’s disease (9, 63–67). These associations indicate that maintenance of CBF in midlife and during the transition into older adulthood is critical to overall brain health and quality of life. In older adults with mild cognitive impairment, the middle cerebral artery pulsatility index (MCA_PI) was reported as significantly higher compared with age-matched controls, suggesting that substantial elevations in MCA_PI may not accompany normal healthy aging, but could instead serve as a marker of subclinical declines in cerebrovascular health (68). In some cases, it has been suggested that intracranial arteries are able to assume some of the buffering burden, characterized by cerebrovascular damping (internal carotid artery PI/MCA_PI) (69). Cerebrovascular damping is a passive phenomenon and describes the ability of intracranial vessels to dampen pulsatile stress to compensate for impaired buffering function in central and neck arteries. With aging, cerebrovascular damping is reduced alongside arterial compliance (70), suggesting that with advancing age there is no inherent compensatory mechanism in the cerebral vasculature to offset the impaired buffering capacity of peripheral conduit arteries (71). Furthermore, cerebrovascular damping may be further impaired in individuals presenting with neurodegenerative conditions (72), pointing to excessive pulsatile stress on the cerebral microvasculature in these populations.

Effects of Resistance Training on Cerebrovascular Function in Young Healthy Adults

Several studies have investigated the effects of RT on cerebral hemodynamic control in young adults, and include both cross-sectional, i.e., resistance-trained individuals and other populations (Table 1) and interventional study designs (Table 2). In a cross-sectional comparison between resistance-trained individuals, aerobic-trained individuals, and healthy age-matched controls, Perry et al. (73) used transfer function analysis [input ABP, output MCA blood velocity (MCAv)] and found that phase was lower in resistance-trained individuals compared with aerobic-trained and untrained controls in response to repeated squat to stands at 0.05 Hz (10-s squat to 1-s stand), but not at 0.1 Hz (5-s squat to 5-s stand) (73). Transfer function analysis-derived phase is an index of the temporal relationship between changes in ABP and MCAv. Although the differences between resistance-trained, aerobic-trained, and untrained groups were marginal, lower phase angle in response to repeated squat-to-stand maneuvers in resistance-trained individuals may be indicative of altered capacity to buffer fluctuations in ABP and thus allow for a faster transmission of increases in ABP into the cerebral circulation (74). Findings from Perry et al. (73) suggest alterations in cerebral autoregulatory function in resistance-trained individuals during 0.05-Hz squat-to-stand maneuvers. However, it is important to note that transfer function analysis-derived measures related to changes in ABP from squat-to-stand maneuvers may not fully capture what is occurring in the cerebral circulation during more intense blood pressure challenges during high-intensity RE.

Table 1.

Cross-sectional/observational studies comparing effects of resistance training on cerebrovascular outcomes (n = 6)

Study (Year)	Study Design and Characteristics	Sample Characteristics	Training Age	Outcome Measures	Findings
Dickerman et al. (2000)	Observational (RT, no control group), acute responses maximum intensity RE	9 elite resistance-trained men aged 31 ± 5 yr	12.3 ± 3.9 yr of RT experience	MCAV	Significant reduction in MCAV from baseline during maximal intensity RE in elite resistance-trained men
Koch et al. (2005)	Observational (RT, no control group), acute responses to RE	39 resistance-trained young adults (17 women aged 24 ± 2.5 yr; 22 men aged 25 ± 2.2 yr)	>6 mo of RT experience	MCAV, MCAPI, MCACVRi, dynamic cerebral autoregulation (phase, gain, coherence)	MCAv remained stable during RE and increased significantly following cessation of RE; MCAPI decreased during RE followed by a drastic increase following cessation of RE; MCACVRi increased consistently throughout duration of RE, followed by a significant drop in MCACVRi following cessation of exercise; coherence and gain decreased during exercise, phase increased marginally during exercise, followed by significant reduction in coherence, gain, and phase in early postexercise period
Xu et al. (2014)	Cross-sectional	59 older adults; 25 older men (15 resistance-trained aged 67.4 ± 10.2 yr); 34 older women (16 resistance-trained aged 66.2 ± 9.3 yr)	Resistance-trained older adults self-reported participating in RT >1× per week	Resting CBF	Significant association between self-reported participation in RT and resting cerebral blood flow in older women but not in men
Perry et al. (2019)	Cross-sectional, acute responses to repeated squat to stand maneuvers (0.05 Hz; 0.10 Hz)	33 young men; 3 young women (12 resistance-trained aged 25 ± 6 yr; 12 aerobic-trained aged 28 ± 9 yr; 12 (3 women) untrained controls aged 26 ± 6 yr)	Resistance-trained young men 6 ± 5 yr of RT experience; Aerobic-trained young men 7 ± 9 yr of AT experience	Dynamic cerebral autoregulation (phase, gain, coherence)	Gain and normalized gain not different between-training groups; phase was lower in resistance-trained young men compared with aerobic-trained and untrained controls during 0.05-Hz squat to stands
Corkery et al. (2021)	Cross-sectional, cerebrovascular reactivity to stepped hypercapnia protocol (3 min at +2, +4, +6% CO2)	39 young men (n = 32) and women (n = 7) (13 resistance-trained aged 24 ± 4 yr; 13 aerobic-trained aged 28 ± 5 yr; 13 untrained controls aged 27 ± 5 yr)	Resistance-trained young adults >1 yr of structured RT experience; Aerobic-trained >1 yr of >150 min of moderate to vigorous AE per week	MCA cerebrovascular reactivity to hypercapnia (change in MCAV in response to change in CO2), MCA cerebrovascular conductance index	Resistance-trained young adults had greater MCA cerebrovascular conductance index at rest and at +2% CO2 compared with aerobic-trained and untrained young adults; no significant differences in cerebrovascular reactivity to hypercapnia between resistance, aerobic, or untrained young adults
Roy et al. (2022)	Cross-sectional, acute responses to repeated squat to stand maneuvers (0.05 Hz; 0.10 Hz)	32 young-to-middle-aged men; 4 young-to-middle aged women (12 resistance-trained aged 24 (18–41) yr†; 12 aerobic-trained aged 26 (18–48)†; 12 (4 women) untrained controls aged 29 (18–33) yr†)	Resistance-trained young men 5.0 (1.5–20.0)† yr of RT experience; Aerobic-trained young men 3.0 (2.0–35.0)† yr of AT experience	Directional sensitivity of the cerebral pressure-flow relationship (ΔMCAvtime/ΔMAPtime or %MCAvtime/%MAPtime)	No between groups differences observed during 0.05-Hz repeated squat to stands; Aerobic-trained and untrained, but not resistance-trained young-to-middle-aged adults showed greater directional sensitivity of cerebral pressure-flow relationship in response to reductions in MAP compared with increases during 0.1-Hz repeated squat to stands

AT, aerobic exercise training; CBF, cerebral blood flow; MCA_CVRi, middle cerebral artery resistance index; MCA_PI, middle cerebral artery pulsatility index; RE, resistance exercise. †Characteristics are reported as medians (ranges) in the study from Roy et al.

Table 2.

Training studies investigating effects of resistance training on cerebrovascular or cerebrovascular-related outcomes (n = 4)

Study (Year)	Study Design and Exercise-Training Characteristics	Sample Characteristics	Outcome Measures	Findings
Suo et al. (2016)	RT + cognitive-training older adults performed 3 sets of 8 repetitions at 80% of 1RM and cognitive training 2 times/wk for 26 wk; RT + sham older adults performed 3 sets of 8 repetitions at 80% of 1RM 2 times/wk for 26 wk; sham + cognitive-training older adults performed stretching and seated calisthenics and cognitive training 2 times/wk for 26 wk; sham-sham controls performed stretching and seated calisthenics 2 times/wk for 26 wk	100 older men (n = 32) and women (n = 68) aged 70.1 ± 6.7 yr (27 RT + cognitive training; 22 RT + sham; 24 sham + cognitive training; 27 sham-sham controls)	Brain structure (gray matter cortical thickness; white matter hyperintensity volume) and function (cognitive function); functional connectivity	RT alone significantly improved global cognition and improved gray matter cortical thickness in the posterior cingulate, RT also reversed progression of white matter hyperintensities in several brain areas compared with cognitive training alone, and sham conditions
Nakamura et al. (2021)	RT group young men performed 4 sets of 10 repetitions in three exercises (leg press, bench press, bent over row) and 3 sets of 10 in three auxillary exercises (knee extensions, shoulder press, biceps curls) 3 days/wk for 8 wk at 75% of 1RM; control group young men were asked to maintain current activity levels	20 previously untrained young men (10 RT aged 23 ± 2; 10 control aged 21 ± 2)	Common carotid artery compliance; internal carotid artery PI; MCAPI; cerebrovascular damping factor (Internal carotid artery PI/ MCAPI)	RT group had significant lower common carotid artery compliance and significantly greater internal carotid artery PI from baseline following 8 wk of RT; MCAPI was unchanged from baseline in RT group; RT group had a significantly greater cerebrovascular damping factor compared with baseline following 8 wk of RT
Thomas et al. (2021 and 2022)	Randomized crossover design; all participants participated in both RT and AT programs with 12-wk washout between each training intervention. RT program involved 3 RE sessions/wk for 12 wk with intensity progressing from 60 to 90% of 1RM over duration of program; AT program involved 2 running sessions and one cycling session/wk for 12 wk with intensity progressing from 60 to 90% of V̇o2 for duration of program	68 previously untrained young men (n = 26) and women (n = 42) aged 25.5 ± 5.4 yr; all 68 participants participated in both RT and AT with 12-wk washout period between each intervention	MCAv; MCAPI; MCACVRi	MCAv and MCAPI significantly reduced following RT but not AT; MCACVRi significantly increased following RT but not AT
Macauley et al. (2022)	Single group periodized RT study; RT program involved 3 RE sessions/wk for 12 wk; periodized program involved 4 mesocycles: mesocycle 1 consisted of 3 sets of 8 repetitions; mesocycle 2 consisted of 3–4 sets of 5–8 repetitions; mesocycle 3 consisted of 3–4 sets of 4 repetitions with intensities approaching 90% of 1RM	20 previously untrained older men (n = 6) and women (n = 14) aged 69.1 ± 5.8 yr	fractional amplitude of low-frequency fluctuations (fALFF), global and regional CBF, white matter hyperintensity volume	12 wk of RT in older adults was significantly associated with reductions in fALFF, improved regional CBF in the hippocampus and posterior cingulate, and small countermeasure effect on the age-related progression of white matter hyperintensity volume

AT, aerobic exercise training; CBF, cerebral blood flow; MCA_CVRi, middle cerebral artery resistance index; MCA_PI, middle cerebral artery pulsatility index; RE, resistance exercise.

In a study using the same sample of habitually trained individuals as Perry et al. (73), Roy and colleagues (75) found that resistance-trained individuals demonstrated a divergence from typical directional sensitivity of the cerebral pressure-flow relationship: ΔMCAv_time/ΔABP_time and %MCAv_time/%ABP_time.

In both aerobic-trained individuals and untrained controls, there was greater sensitivity to acute reductions in ABP compared with increases in ABP, whereas there were no differences in directional sensitivity of the cerebral pressure-flow relationship in chronically resistance-trained individuals (75). This finding may relate to the increased arterial stiffness observed in the neck arteries of resistance-trained individuals. Specifically, perhaps increased arterial stiffness in resistance-trained individuals keeps cerebral perfusion pressure elevated, allowing cerebral blood flow to be better maintained during substantial drops in ABP compared with other populations, where reductions in ABP are observed to elicit significant reductions in CBF. The exact mechanisms influencing directional sensitivity in the cerebral pressure and flow relationship are not fully understood; however, the frequent exposure to both marked increases and decreases in ABP in resistance-trained individuals may lead to adaptations in the heart allowing for better maintenance of cardiac output during significant RE- or post RE-induced blood pressure challenges to ensure stable delivery of CBF compared with those not engaged in RT (76).

A study by Koch et al. (77) investigated cerebral hemodynamics and dynamic cerebral autoregulatory function during and immediately following RE in young resistance-trained men and women (>6 mo of RT) and reported several key findings. In response to acute RE, young resistance-trained individuals demonstrated a significant increase in ABP and no change in MCAv, leading to increased middle cerebral artery resistance index (MCA_CVRi) during exercise, effectively attenuating the effects of increased ABP on the cerebral vasculature (77). This study also observed a significant decrease in MCA_PI during exercise, followed by a significant increase in MCA_PI occurring alongside a significant drop in ABP immediately post-RE. Interestingly, both MCAv and MCA_CVRi dropped significantly immediately post exercise in parallel with ABP below pre-RE levels during the early recovery stage. These patterns of changes in MCA_CVRi and MCA_PI immediately following RE, taken together, align with patterns observed in presyncope and syncope (increased MCA_PI; decreased MCA_CVRi) (77). Koch et al. (77) interpret their findings in this sample of resistance-trained individuals as a reflection of a rapid reduction in cerebrovascular resistance via vasodilation at the arteriole level. This vasodilation may act to counterbalance the sudden and severe reductions in ABP post-RE while peripheral and conduit arteries continue to produce high resistance to ensure that cerebral perfusion pressure (ABP intracranial pressure) is kept stable (77). Furthermore, transfer function analysis revealed signs of a temporary disturbance in dynamic cerebral autoregulatory function in resistance-trained individuals, revealing significant elevations in low-frequency power of both ABP and MCAv, as well as a significantly reduced phase angle during the early recovery phase following an acute bout of RE. Both increased low-frequency power and reduced phase angle point to a temporary disturbance in autoregulatory function. Increased low-frequency power of both ABP and MCAv suggests that the magnitude of changes in ABP had greater influences on changes in MCAv while significantly increased phase suggests that these changes are being transmitted to the cerebral circulation significantly faster compared with during or post-RE (77). The authors acknowledge that the interpretation of increased low-frequency power and reduced phase angle immediately post-RE directly conflicts with the interpretation of the findings related to MCA_CVRi and MCA_PI. The authors suggest that the transfer function analysis-derived outcomes imply increased sympathetic tone and a subsequent upstream cerebrovascular vasoconstriction immediately post-RE, whereas the MCA_CVRi and MCA_PI responses post-RE imply a vasodilatory response (77). The reasoning for conflicting results and interpretation is unclear, however, may be tied to incorrect methodology related to the assessment of dynamic cerebral autoregulation during forced oscillations in ABP. Current assumptions that need to be met for transfer function analysis-based assessment of dynamic cerebral autoregulation require 5 min of continuous forced oscillations in ABP, and consistent frequency bands for oscillations in ABP (78). These assumptions are the primary reason for the repeated squat-to-stand model being the optimal approach for the assessment of cerebral autoregulation. In the study by Koch et al. (77) individuals were asked to perform eight repetitions of 80–90% of their one repetition maximum over a duration of ∼1 min, far below the 5-min threshold necessary for transfer function analysis. In addition, the frequency bands reported in this study were mentioned to range between 0.04 and 0.14 Hz (77). This range includes overlap between the very low-frequency band (0.02–0.07 Hz) and low-frequency bands (0.07–0.2 Hz) but were analyzed together. As such, the findings from Koch et al. (77) related to cerebral autoregulation must be interpreted carefully. Taken together, the authors proposed that these findings suggest that in response to the sudden and substantial reduction in ABP immediately following RE, the cerebral circulation triggers an “emergency reaction” to stabilize CBF and prevent syncope, even though dynamic cerebral autoregulation appears to be disrupted. It is important to highlight that the resistance-trained individuals in the study from Koch et al. (77) included individuals who had at least 6 mo of RT experience but provided little information on key characteristics of the sample such as RT frequency, typical workloads (i.e., intensity), type of exercise being performed (i.e., free weight vs. machine), or precise training age. In addition, no comparator groups were included in the study from Koch et al. (77), further complicating interpretation. Thus, the observations from this study, although informative, may not be entirely indicative or characteristic of chronic cerebrovascular adaptations to high-intensity RT and should be interpreted while keeping in mind the aforementioned limitations.

In a training study conducted by Thomas et al. (79), 68 young healthy adults participated in 3 mo of both AT and RT. In this study, RT was not shown to have any effect on dynamic cerebral autoregulatory function, whereas AT was associated with reduced coherence during spontaneous oscillations in ABP in the low-frequency range (0.07–0.2 Hz). Coherence is a transfer function analysis-derived measure that characterizes linearity between changes in ABP and MCAv. Although no significant effects of 3 mo of RT on dynamic cerebral autoregulation were observed, RT was associated with increased ABP and reduced MCAv at rest, therefore resulting in a significant elevation in resting MCA_CVRi in the resistance-trained group. The authors also observed a significant reduction in resting MCA_PI in the resistance-trained group (79). The reduction in pulsatility in resistance-trained individuals conflicts with other literature (80). However, it must be noted that studies observing increased MCA_PI in resistance-trained individuals were cross sectional, and while the sample was defined as young men who had participated in vigorous RT for >2 yr, >5 times/wk, “vigorous” was undefined and information regarding the type of RT was not provided. Thus, the relationship between RT and increased pulsatility in the work from Nakamura et al. (80) should be interpreted carefully. The findings from Thomas et al. showing that 3 mo of RT is associated with reduced MCA_PI and increased MCA_CVRi at rest may point to a compensatory adaptation within the cerebral vasculature (79). Despite potential reductions in central arterial compliance with RT (not assessed by Thomas et al.) where an increase in blood flow pulsatility in cerebral vessels is to be expected, MCA_PI is reduced, perhaps suggesting improved buffering capacity of intracranial vessels when the function of extracranial conduit arteries may be compromised. Furthermore, a significant elevation in MCA_CVRi may also point to compensatory adaptations to further protect the cerebral microvasculature, as increased resistance at the level of arterioles may result in attenuated transmission of high-pressure and pulsatile blood flow to microvasculature directly supplying neural tissues. It is important to emphasize, however, that this interpretation is speculative and requires further study, as MCA_CVRi is an indirect surrogate measure of cerebrovascular resistance calculated using systemic ABP and an index of CBF (ABP/MCAv) instead of the direct measurement approach for cerebrovascular resistance (cerebral perfusion pressure/CBF) (69). Taken together, these adaptations may provide additional protection for cerebral microvasculature and the brain such that increases in arterial stiffness (and thereby impaired buffering function) in the aorta and neck arteries may be effectively countered by improved compliance of intracranial arteries (reduced MCA_PI) and changes in vascular tone at the arteriolar level (increased MCA_CVRi).

Findings from a separate study led by Nakamura et al. (81), support the notion of compensatory mechanisms in intracranial vessels in resistance-trained individuals. Following 8 wk of RT in healthy young men, they observed no changes in MCA_PI despite a significant increase in internal carotid artery PI and a reduction in carotid artery compliance. Furthermore, individuals in the RT group were observed to have significantly greater cerebrovascular damping factor (internal carotid artery PI/MCA_PI) compared with control subjects (81). In the study from Nakamura and colleagues (81), improved cerebrovascular damping factor following 8 wk of RT compared with control subjects makes a compelling case for the adaptive capacity of cerebral vasculature. Improved cerebrovascular damping factor may point to a potential protective adaptation, ensuring cerebral small vessels and neural tissues are protected from high-pressure and pulsatile hemodynamic stress secondary to increases in central and neck artery stiffness. Adaptations in intracranial artery function may also be supported by findings from Dickerman et al., who investigated cerebral hemodynamic responses to high-intensity (near or at 1 repetition maximum) RE in young-to-middle-aged elite male power athletes (26–40 yr old). This study observed a 25% drop in MCAv in response to maximal RE (82), perhaps supporting increased MCA_CVRi in RT individuals.

The acute and sudden drop in MCAv in response to RE in the group of elite resistance-trained individuals from Dickerman et al. (82) conflicts with many acute studies in untrained individuals reporting increases in MCAv during acute RE. Findings from Dickerman et al. (82) may point to adaptations in cerebral hemodynamic control at the far end of the resistance-training spectrum to dampen or reduce cerebral perfusion during acute and severe RE-induced hypertensive challenges despite potential reductions in conduit artery compliance, although compliance was not measured in this group of elite lifters. However, this requires further investigation including more rigorous experimental approaches, as changes in arterial blood gases [oxygen and carbon dioxide; potent regulators of cerebral hemodynamics (83)], were not reported in the study from Dickerman and colleagues (82). Furthermore, Dickerman et al. (82) did not report whether the Valsalva maneuver (VM) was elicited during maximal leg press exercise. Based on the population (elite experienced weightlifters) and intensity (100% of 1 repetition maximum), the VM was likely to influence cerebral hemodynamic responses observed in this study, as during intense RE, the VM is involuntary at ≥80% of a subjective one repetition maximum (1 repetition maximum) (43). The relationship between cerebral hemodynamics and the VM has been well-reviewed by Perry et al. (73) and thus will not be covered comprehensively in the present review (43). Briefly, VM is a technique often elicited during heavy RE, involving a forceful exhalation against the closed glottis to elicit a marked increase in intrathoracic pressure, intra-abdominal pressure, and intracranial pressure, thereby resulting in inhibited venous return and elevated cerebral perfusion pressure (84). In response to the VM, there is an initial increase in MCAv commensurate with the increases in ABP in the first 5 s, followed by a significant suppression in both MCAv and ABP after this point. Thus, the reduction in MCAv reported in the work from Dickerman et al. (82) may be representative of the eventual reductions in ABP and CBF in response to the VM. In this group of elite lifters, it is reasonable to speculate that the VM was elicited immediately before the initial concentric phase of the maximum effort leg press exercise, leading to reductions in MCAv.

Although significant increases in ABP during high-intensity RE can stress cerebral conduit arteries and cerebral vasculature, elevations in ABP may not elicit detrimental effects on the vasculature if pressure surrounding those arteries is similarly elevated. The ratio between pressure inside the artery and pressure outside of the artery, transmural pressure, has been proposed to be the stimulus most responsible for eliciting damage to the cerebral vasculature during hypertensive challenges (85). Thus, the VM may serve as a cerebrovascular-protective involuntary mechanism by increasing intra-abdominal pressure and intracranial pressure, thereby reducing transmural pressure and attenuating the effects of RE-induced hypertension on cerebral conduit arteries and cerebral vasculature (85). Perhaps long-term habitual lifters, who elicit the VM frequently during exercise sessions, can avoid or attenuate detrimental effects of RT on arterial stiffness and compliance that have been frequently reported in training studies with previously untrained individuals participating in structured RT for the first time. Techniques used during RE may therefore be an important regulator of alterations in vascular and cerebrovascular function. Future work should aim to conduct training intervention studies in which participants partake in RT both with and without VM to further explore mechanisms underlying how RT impacts arterial stiffening and cerebral hemodynamics.

Adaptations in intracranial vessels, potentially in response to increased stiffness in conduit arteries are also supported by cross-sectional findings from Corkery et al. (86), as resistance-trained individuals were observed to have greater cerebrovascular conductance index (an indirect measure of the ease of cerebral blood flow at a given pressure, calculated as MCAv/ABP) when compared with aerobic-trained individuals in this study. The mechanisms underpinning greater cerebrovascular conductance index in resistance-trained individuals are unclear, however, the authors speculate one possible explanation is the diversity of stimuli that individuals are exposed to with participation in a typical resistance program (86). When compared with AE, which typically involves long periods of similar movement patterns, a typical RE session is accompanied with several different exercises, targeting several different muscle groups, complex movement patterns, and differing intensities. The complexity of a typical RE session may present and manifest itself as a greater cognitive and cerebral metabolic challenge compared with steady-state AE. Although more study is necessary, the diversity of stimuli and movement patterns taken alongside the heavy emphasis on lifting form and technique in RT may elicit adaptations in neurovascular coupling-related mechanisms to improve cerebral perfusion during periods of elevated metabolic demand (i.e., cognitive testing) in resistance-trained individuals.

The studies discussed earlier provide important insights into the effects of RT on brain blood flow regulation (i.e., dynamic cerebral autoregulation, cerebrovascular function, and mechanical properties of cerebral vessels). However, it is still uncertain if individuals who participate in RT exhibit altered cerebral hemodynamic control to more drastic oscillations in ABP similar to those that would be experienced during high-intensity RE. Perhaps resistance-trained individuals experience unique adaptations in response to frequent exposure to extreme changes in ABP, beyond what can be forced using current approaches (i.e., repeated squat-to-stand maneuvers). Thus, to attempt to more clearly delineate cerebral hemodynamic regulatory mechanisms in resistance-trained individuals compared with other populations, the stimulus administered in experimental designs may need to be more representative of the training stimulus eliciting potential adaptations in cerebral hemodynamic control. Future studies may accomplish this by forcing more substantial increases in ABP than what has been examined using current experimental approaches.

Available evidence supports adaptations in cerebral hemodynamic control with RT in young healthy individuals. Both Roy and Perry et al. observed differences in cerebral autoregulatory and cerebral pressure-flow-related indices in response to repeated squat-to-stand maneuvers between resistance-trained individuals and control populations (73, 75).

Roy et al. (75) observed similar sensitivity of changes in MCAv in response to both increases and decreases in ABP in resistance-trained subjects, whereas untrained controls demonstrated greater sensitivity of changes in MCAv in response to reductions in ABP, perhaps pointing to a cerebrovascular-protective adaptation as with RT, as those who participate in RT are more frequently exposed to large oscillations in ABP. These findings may suggest that resistance-trained individuals present with an improved capacity to adjust CBF in response to both increases and decreases in ABP compared with other populations (75). Perry et al. observed an altered temporal relationship (reduced phase angle) where changes in ABP are more quickly transmitted to the cerebral circulation between resistance-trained individuals compared with control populations. This finding is in line with the understanding of the impaired buffering function of neck arteries in resistance-trained individuals. In other studies, cerebrovascular adaptations to RT appear to follow a common thread, where cerebral vessels demonstrate an improved capacity to buffer high-pressure and pulsatile blood flow being delivered into the cerebral circulation via conduit arteries (reduced MCA_PI, improved cerebrovascular damping factor) (77, 79, 81). In addition, multiple studies report increased MCA_CVRi in resistance-trained individuals (77, 79), potentially another compensatory mechanism at the arteriolar level to prevent high-pressure and pulsatile blood flow from reaching fragile cerebral microvessels. It must be reiterated, however, that MCA_CVRi is an index of cerebrovascular resistance calculated using systemic ABP (ABP/MCAv) and thus must be interpreted with caution (69). The available evidence, taken alongside the understanding that RT has been frequently shown to be associated with reduced carotid artery compliance, does indeed point to potential compensatory cerebrovascular adaptations for the protection of cerebral microvasculature and tissues in young healthy adults.

Acute Cerebrovascular Responses to Resistance Exercise in Older Adults

Although the literature surrounding chronic alterations in cerebral hemodynamic control with RT in older adults is scarce, some studies investigating acute cerebrovascular responses to RE in older adults may provide valuable insight into underlying mechanisms and the potential interactions between RT-related adaptations and age. Rosenberg et al. (87) showed that older men and women had a significantly lower increase in MCAv immediately following cessation of high-intensity isokinetic knee flexion and extension compared with young adults. This study also observed greater carotid β-stiffness and greater transmission of pulsatile blood velocity (inverse of cerebrovascular damping factor; MCA_PI/carotid PI) into the cerebral circulation in untrained older adults compared with untrained young adults following RE (87). In a recent study involving older men and women, Marôco et al. (88) observed distinct sex differences in post-isokinetic RE cerebral hemodynamics. This study found that following maximal isokinetic knee flexion and extension exercise, MCAv increased in women, but not in men. Older men also had a significantly greater increase in carotid artery PI, MCA_PI, and a significantly lower cerebrovascular conductance index post-RE compared with older women. These results support the relationship between age-related conduit artery stiffening and subsequent transmission of pulsatile blood flow to the cerebral circulation.

Effects of Resistance Training on Cerebrovascular Health and Function with Aging

When compared with younger adults, there is little evidence available supporting increased arterial stiffness or reduced arterial compliance with RT in middle-aged and older adults (28, 37–39). There is however a clear aging effect on the vasculature, in which arteries become stiffer and less compliant with age (4, 5). While RT-related reductions in compliance are not observed in middle-aged and older adults, perhaps the chronic cerebrovascular adaptations to RT may still counter age-related stiffening and its impacts on the brain over the life course. A summary of how participation in RT may interact with age-related arterial stiffening can be seen in Fig. 1.

Figure 1.

Summary schematic of the effects of resistance training (RT) in young healthy adults (A) and older adults (B). Schematic summarizes that findings from literature are mixed as it relates to RT-induced changes in arterial structure (stiffness) and function (compliance). In older adults, where increases in arterial stiffness and decreases in arterial compliance occur with normal aging, there is no evidence suggesting that RT is associated with deleterious effects on the vasculature. Furthermore, RT in older adults is associated with several positive benefits as it relates to cerebrovascular and overall brain health, including improved cerebral blood flow (CBF), cognitive function, and brain structure. Elements of this figure were created with a licensed version of Biorender.com.

A 6-mo RT study in older adults observed RT-related protection from age-related cortical gray matter atrophy and demonstrated marginal reversal of white matter hyperintensity burden (40). Both gray matter atrophy and accumulation of white matter hyperintensities are observed in normal brain aging and have strong associations with neurodegenerative disorders including mild cognitive impairment, vascular dementia, Parkinson’s disease, and Alzheimer’s disease (9, 63–67), making potential antiaging effects of habitual RT of clinical interest. Improved white matter integrity with RT is also supported by the previously mentioned study from Xu et al. (42), as self-reported participation in RT was associated with significantly lower white matter hyperintensity burden compared with age-matched sedentary controls. The attenuation of age-related degradation in brain structure with RT in older adults directly conflicts with the pathology-based interpretation of the effects of increased arterial stiffness and decreased arterial compliance on cerebral circulation and overall brain health. Beyond protection from age-related structural changes in the brain, there is also evidence that supports significant improvements in brain function associated with RT in older adults (40, 41). Cognitive benefits of RT include improved global cognition, executive function and working memory, cognitive domains that are particularly impaired with advancing age (40, 41, 89). The findings of both maintained or improved brain structure and function in older adults who participate in RT further emphasize the need for a nuanced interpretation of RT-related stiffening.

Considering the effects of aging on cerebrovascular function (increased CBF pulsatility, impaired cerebrovascular damping factor) alongside the cerebrovascular adaptations to RT (reduced CBF pulsatility, improved cerebrovascular damping factor), RT may potentially mitigate the effects of age-related arterial stiffening on the cerebral vasculature and neural tissues. The direct effects of RT on cerebral hemodynamics and specific cerebrovascular regulatory mechanisms in older adults remain understudied. However, given the lack of evidence supporting increased arterial stiffness in middle-aged and older adults who engage in RT (28, 37–39), there does not appear cause for concern with respect to cerebrovascular health when it comes to promoting RT in midlife and older adulthood.

Methodological Considerations for Future RT Studies

Many factors may influence observed adaptations to RT. Although cerebrovascular adaptations to RT remain understudied, information from studies investigating the effects of RT on stiffness and compliance can provide valuable insight into how different training stimuli may affect the vasculature. The intensity at which RE is performed appears to be a major determinant in dictating whether changes in vascular structure or function are observed. Multiple studies have observed no significant changes in arterial stiffness or compliance when RT was performed at low-to-moderate intensities (∼50–70% of 1 repetition maximum) (90–92), whereas RT performed at intensities greater than 75% of one repetition maximum are associated with increases or reductions in stiffness and compliance, respectively (30, 32–35). The mechanisms by which low-to-moderate intensity RT is able to avoid vascular stiffening are likely associated with the relationship between physical effort and the proportional change in ABP. In addition, in RT studies using higher intensities, weightlifting techniques such as the VM are not reported, and thus it is unclear whether participants in these studies are eliciting the potential protective effects of the VM or if they are coached to breathe through high-effort lifts. The type of RT being performed also appears to have significant implications on vascular adaptations. Multiple works from Okamoto et al. have worked to uncover different mechanisms that may lead to increases and reductions in stiffness and compliance, respectively (34, 93, 94). These studies observed significant stiffening and elevations in plasma norepinephrine (vasoconstrictor) in healthy young adults in response to upper body RT, but not lower body RT (33). Why upper body RT may elicit stiffening and greater sympathetic outflow compared with lower body RT is unclear and requires further study. The same research group also conducted two experiments related to muscular contraction timing or tempo during RT. The first study found that slow eccentric but fast concentric RT at 80% of one repetition maximum was not associated with elevations in arterial stiffness, whereas slow concentric but fast eccentric RT was significantly associated with elevations in stiffness (94). This finding likely points to the time under tension (concentric contraction time) and the associated sustained effort and strain being an important factor for determining changes in vascular structure and function. Similarly, the second study found that slow concentric and slow eccentric RT at lower intensities (40% of 1 repetition maximum) was also able to avoid the stiffening effects of RT (93). It is unclear whether these effects are a product of the tempo of each individual repetition or lower training intensity. As previously mentioned, RT at lower intensities has been shown to be able to preserve arterial elasticity independent of muscle contraction timing (90–92). Changes in conduit artery structure and function associated with RT are also affected by the timing or periodization of RT programs. In a separate study from Okamoto et al. (35) comparing the effects of intermittent and continuous RT programs, individuals in the intermittent RT group were asked to participate in 3 cycles of 4 wk of RT and 2 wk of detraining, for a total of 16 wk. In this study, authors observed lower levels of stiffening in the intermittent RT group compared with continuous RT (35). These findings suggest that even at higher intensities (75% of 1 repetition maximum), periodic deloading or extended rest periods of ∼2 wk can attenuate some of the stiffening effects of RT, whereas the improvements in muscular strength and muscle mass remained the same between intermittent and continuous RT groups (35).

While the methodological considerations related to RT programming mentioned earlier are specific to studies investigating vascular stiffness and compliance, their implications may extend to the cerebral vasculature. If cerebrovascular adaptations to RT are compensatory in nature, perhaps the changes in cerebrovascular function are only evident in response to training stimuli that elicit vascular stiffening in the peripheral conduit arteries. However, it is important to consider that the cerebral vasculature responds uniquely and independently to hemodynamic stress compared with peripheral vasculature (95). Thus, although the effects of peripheral vascular adaptations to RT do indeed influence cerebrovascular control, the stimuli eliciting said peripheral adaptations are still likely to be received differently by the cerebral circulation. While to our knowledge, there is no available evidence related to the effects of different training intensities, duration, contraction timings, or periodization practices on cerebrovascular function, the available evidence related to arterial stiffness and compliance is sufficient for hypothesis generation and informing the design of future studies investigating cerebrovascular adaptations to different RT programs.

It is also important to address limitations in the evidence related to cerebrovascular adaptations to RT across the aging spectrum. Currently, much of the literature concerning adaptations in cerebral hemodynamic control with RT involves the use of systemic ABP (most often measured at the finger via photoplethysmography) as a surrogate for cerebral perfusion pressure, making interpretation of changes in measures such as cerebrovascular conductance index and cerebrovascular resistance inherently limited. More accurate characterization of the hemodynamic stress on the brain during RE or chronic alterations in cerebral perfusion pressure regulation is technically and ethically challenging, however, as a direct measure of cerebral perfusion pressure requires invasive measurement (intraventricular catheter) of intracranial pressure (96). Furthermore, the assessment of changes in cerebrovascular function using transcranial Doppler ultrasound is accompanied with several limitations as well, particularly as it relates to structural changes in cerebral vessels. Transcranial-Doppler ultrasound allows for the noninvasive measurement of cerebral blood velocity, however, provides no structural information related to cerebral vessels (97). Thus, it is not possible to determine if MCA resting diameter or vasoreactivity is altered with habitual RT with the use of transcranial Doppler ultrasonography. Other imaging and analysis approaches such as magnetic resonance imaging would allow for the assessment of both structural and functional alterations cerebrovascular with habitual RT, allowing for a more robust and informed interpretation of the effects of RT on the cerebral vascular system.

Future Directions

Based on the literature synthesized in the current review, we wish to emphasize the following takeaway points. Overall, there is a significant lack of literature related to acute responses to exercise in older adults. Independent of chronic adaptations, the cerebrovascular responses to acute RE in older adults are not well understood. Additional research focusing on acute cerebrovascular responses to RE in older adults will provide a stronger understanding of how RE affects cerebrovascular function, particularly with increased uptake in RE prescription for older adults. This review also highlights the need for RT studies in older adults to determine the long-term implications of RT on cerebrovascular function and brain health. While RT is associated with improved CBF and cognition, and slows down brain atrophy, the mechanisms underlying these adaptations remain unclear. Whether RT-related adaptations in cerebral hemodynamics and control of CBF observed in young healthy adults are consistent with adaptations potentially occurring in resistance-trained older adults remains unknown. More studies should seek to differentiate the effects of habitual AT and RT on vascular and cerebrovascular function across the lifespan, to better understand interactions between exercise and the normal aging process with respect to chronic vascular adaptations.

Future study design should also account for sex differences in the effects of RT on arterial compliance and stiffness, and cerebral hemodynamic control. Few studies have explored sex differences in the context of cerebrovascular adaptations to RT. Furthermore, there should be a greater focus on the interaction between peripheral vascular and cerebrovascular function, RE and RT, and in women specifically across the lifespan.

Researchers should also aim to differentiate RT-related stiffening or reductions in compliance and age- and disease-related stiffening and respective underlying mechanisms. There is also a need for understanding how different RT protocols may lead to different adaptations, and how the VM may affect these adaptations. RT intensity, muscular contraction timing, training duration, periodization, type of RT performed, and use of different lifting techniques may all have significant implications on potential vascular and cerebrovascular adaptations. While challenging to conduct, longitudinal studies may serve an instrumental role in advancing our understanding of the effects of RT on cerebral hemodynamic control across the aging spectrum.

Much of our current knowledge about the long-term effects of RT comes from cross-sectional studies, leaving it difficult to discern cerebrovascular adaptations specific to prolonged RT. Despite the limitations of cross-sectional study design, characterizing hemodynamic responses in elite athletes may help to uncover the effects of long-term adaptations to different exercise types. Recruitment of lifelong exercisers, both aerobic and resistance, can provide critical insight into the adaptations that occur at the far ends of the exercise spectrum. As RT becomes an increasingly popularized method of exercise, particularly in older adults as a method to counter age-related physical decline and frailty, furthering our understanding of its effects on cerebral vasculature and overall brain health is of importance. Indeed, this research area is understudied and requires additional work to elucidate the effects of RT on cerebral hemodynamic control and related cerebrovascular and brain-health endpoints.

CONCLUSION

Evidence from resistance-trained participants across young, midlife, and older adults suggests that RT-induced adaptations to larger peripheral arteries may not elicit detrimental effects on cerebral blood flow control. These findings challenge current contemporary views on RT-related arterial stiffening and reduced compliance and the potential consequences on brain blood flow control (summarized in Fig. 1). In middle-aged and older adults, evidence suggests that participation in RT is not associated with changes in compliance or stiffness (28, 37–39), though cross-sectional studies show greater stiffness in middle-aged adults who habitually RT compared with controls (98). RT is also associated with improved CBF (41, 42), improved brain function (40, 41), and protection from age-related atrophy of neural tissues (40) in older adults. Based on these findings, there is currently no evidence supporting the detrimental effects of RT on the brain, particularly in older adults. Indeed, it seems that RT into older adulthood is associated with strictly positive outcomes and may help combat age-related decline not only in the brain, but also in overall cardiometabolic, muscle, and bone health (23).

While RT is associated with improvements in cerebrovascular-related endpoints, it remains unclear what adaptations may occur in the cerebral vasculature in older adults with habitual RT. In untrained older adults, reduced arterial compliance was associated with increased MCA pulsatility (87). Although there are no data on the effects of RT on cerebrovascular pulsatility in older adults, in young healthy adults, many reports suggest that RT is not only associated with reduced arterial compliance (30, 32–35) but also with increased cerebrovascular resistance (77, 79), reduced cerebrovascular pulsatility (77, 81), and altered autoregulatory function (73, 75, 77, 79). These findings may suggest compensatory mechanisms in place with habitual RT, where intracranial vessels are able to partially buffer high systolic pressures and pulsatile blood flow when supply arteries (i.e., aorta, carotid arteries) are compromised to protect fragile cerebral microvasculature. The improved buffering function of intracranial arteries to protect cerebral microvessels may lead to an avoidance of cerebrovascular dysfunction-related hypoperfusion of neural tissues. Further study is necessary to determine whether these cerebrovascular adaptations to RT hold true in older adults, or if differential adaptive mechanisms exist with aging to protect the brain from hypertensive challenges during RT.

Nonetheless, based on the current landscape of evidence discussed in the present review, RT-related arterial stiffening does not seem to be associated with negative effects on the brain as one would expect based on the contemporary understanding of arterial compliance and stiffness.

GRANTS

E.Y.A. is supported by a Natural Sciences and Engineering Research Council (NSERC) Postgraduate scholarship doctoral award. This review is supported by an NSERC Discovery Grant held by B.K.A.

DISCLOSURES

No conflicts of interest, financial or otherwise, are declared by the authors.

AUTHOR CONTRIBUTIONS

E.Y.A. and B.K.A. conceived and designed research; analyzed data; interpreted results of experiments; prepared figures; drafted manuscript; edited and revised manuscript; approved final version of manuscript.