The number of adults with Alzheimer’s disease (AD) or related dementia is expected to increase exponentially. Interventions aimed to reduce the risk and progression of AD and dementia are critical to the prevention and treatment of this devastating disease. Aging and cardiovascular disease risk factors are associated with reduced vascular function, which can have important clinical implications, including brain health. The age-associated increase in blood pressure and impairment in vascular function may be attenuated or even reversed through lifestyle behaviors. Greater volumes of habitual exercise and higher cardiorespiratory fitness are associated with beneficial effects on vascular health and cognition. Exercise and cardiorespiratory fitness may be most important during midlife, as physical activity and cardiorespiratory fitness during the middle-aged years are associated with future cognitive function. The extent to which exercise, and more specifically aerobic exercise, influences the cerebral circulation is not well established. In this review, we present our working hypothesis showing how cerebrovascular function may be a mediating factor underlying the association between exercise and cognition, as well as discuss recent studies evaluating the effect of exercise interventions on the cerebral circulation.

Exercise is associated with higher cognitive function and is a promising intervention to reduce the risk of dementia. With advancing age, there are changes in the vasculature that have important clinical implications for brain health and cognition. Primary aging and vascular risk factors are associated with increases in arterial stiffness and pulse pressure, and reductions in peripheral vascular function. Objective: The purpose is to discuss the epidemiological, observational, and mechanistic evidence regarding the link between age-related changes in vascular health and brain health. Methods: We performed a literature review and integrated with our published data. Results: Epidemiological evidence suggests a link between age-related increases in arterial stiffness and lower cognitive function, which may be mediated by cerebral vascular function, including cerebral vasoreactivity and cerebral pulsatility. Age-associated impairments in central arterial stiffness and peripheral vascular function have been attenuated or reversed through lifestyle behaviors such as exercise. Greater volumes of habitual exercise and higher cardiorespiratory fitness are associated with beneficial effects on both peripheral vascular health and cognition. Yet, the extent to which exercise directly influences cerebral vascular function and brain health, as well as the associated mechanisms remains unclear. Conclusion: Although there is evidence that exercise positively impacts cerebral vascular function, more research is necessary in humans to optimize experimental protocols and address methodological limitations and physiological considerations. Understanding the impact of exercise on cerebral vascular function is important for understanding the association between exercise and brain health and may inform future intervention studies that seek to improve cognition.

The central arteries dampen the pulsatile forces from myocardial contraction, limiting the pulsatility that reaches the cerebral vasculature, although there are limited data on this relationship with aging in humans. The purpose of this study was to determine the association between aortic stiffness and cerebral artery pulsatility index in young and older adults. We hypothesized that cerebral pulsatility index would be associated with aortic stiffness in older adults, but not in young adults. We also hypothesized that both age and aortic stiffness would be significant predictors for cerebral pulsatility index. This study included 23 healthy older adults (aged 62 ± 6 years) and 33 healthy young adults (aged 25 ± 4 years). Aortic stiffness was measured using carotid-femoral pulse wave velocity (cfPWV), while cerebral artery pulsatility index in the internal carotid arteries (ICAs), middle cerebral arteries (MCAs), and basilar artery were assessed using 4D Flow MRI. Cerebral pulsatility index was calculated as (maximum flow – minimum flow) / mean flow. In the combined age group, there was a positive association between cfPWV and cerebral pulsatility index in the ICAs (r = 0.487; p < 0.001), MCAs (r = 0.393; p = 0.003), and basilar artery (r = 0.576; p < 0.001). In young adults, there were no associations between cfPWV and cerebral pulsatility index in any of the arteries of interest (ICAs: r = 0.253; p = 0.156, MCAs: r = −0.059; p = 0.743, basilar artery r = 0.171; p = 0.344). In contrast, in older adults there was a positive association between cfPWV and cerebral pulsatility index in the MCAs (r = 0.437; p = 0.037) and basilar artery (r = 0.500; p = 0.015). However, the relationship between cfPWV and cerebral pulsatility index in the ICAs of the older adults did not reach the threshold for significance (r = 0.375; p = 0.078). In conclusion, age and aortic stiffness are significant predictors of cerebral artery pulsatility index in healthy adults. This study highlights the importance of targeting aortic stiffness in our increasingly aging population to reduce the burden of age-related changes in cerebral hemodynamics.

Habitual exercise may influence the cerebral hemodynamics, as it affects other variables of vascular health in this population. We report that habitual exercise training does not influence cerebrovascular reactivity in young adults, as there were no significant differences between aerobic-trained, resistance-trained, and untrained individuals. Despite this finding, the mode of habitual exercise training had a moderate influence on resting cerebral hemodynamics such that resistance-trained adults had greater cerebrovascular conductance compared with aerobic-trained adults.

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