Regular articleHearts and minds: linking vascular rigidity and aerobic fitness with cognitive aging
Introduction
Aging is associated with decreased performance across a variety of cognitive domains, and executive functions are thought to be particularly affected (Park and Reuter-Lorenz, 2009). The physiological changes underlying this decline are still under investigation, but studies have shown that markers of poor vascular health are associated with decreased cognitive performance (Bos et al., 2012, Brown et al., 2010, Girouard and Iadecola, 2006, Kearney-Schwartz et al., 2009, Mitchell et al., 2011, Zhong et al., 2014). There is therefore much to gain from understanding the link between age-related cognitive decline and declining vascular health, as well as the influence of modulating factors such as cardiorespiratory fitness, which may provide an avenue for successful intervention.
As we age, large arteries become stiffer, thereby increasing pulse pressure, the amplitude of the reflected wave and the pulsatility of smaller downstream vessels (O'Rourke and Hashimoto, 2007). The ascending aorta plays a predominant role in cardiac pulsation dampening so is thought to be the first and worst affected artery in the body (Fritze et al., 2012, Redheuil et al., 2010). It may therefore be the most sensitive marker of early arterial damage in otherwise healthy adults.
Because of its high baseline blood flow, the brain is one of the only organs in the body to experience pulsatile flow. This renders the brain more sensitive to the effects of age-related large artery stiffening (Laurent and Boutouyrie, 2007, O'Rourke and Hashimoto, 2007, Sierra et al., 2004). Increased pulse-wave velocity at the level of the aorta, possibly through increases in carotid pulsatility (Mitchell et al., 2011), has been shown to be associated with cerebral damage such as decreased brain volumes (Bos et al., 2012, Mitchell et al., 2011) and increased white matter hyperintensity (WMH) volumes (Bos et al., 2012, Choi et al., 2013, Mitchell et al., 2011, Rosano et al., 2013, van Elderen et al., 2011). This damage may have functional significance, because increased central pulse-wave velocity in older adults was found to be associated with decreased cognitive performance (Bos et al., 2012, Kearney-Schwartz et al., 2009, Mitchell et al., 2011, Zhong et al., 2014).
Large artery damage, especially when it occurs in conjunction with white matter vascular lesions, is likely to be also associated with poorer cortical vascular health. Cerebrovascular reactivity (CVR) is reduced in several diseases known to include vascular damage and changes in neurovascular coupling, such as stroke, dementia, and diabetes (Girouard and Iadecola, 2006, Gorelick et al., 2011, Iadecola, 2010, van Elderen et al., 2011). Furthermore, we and others have previously shown that healthy older adults show decreased blood oxygenation level dependent (BOLD) and flow CVR to CO2 as compared with young adults (Bailey et al., 2013, Gauthier et al., 2013, Liu et al., 2013, Lu et al., 2011). However, although there is mounting evidence that vascular health and cognitive performance are related in older adults, the strength, as well as the temporal and spatial characteristics of this vascular impairment progression, and its influence on decline in specific cognitive domains remain to be determined.
Lifestyle factors can modulate age-related vascular changes (Savela et al., 2010). A healthy diet and regular exercise are the most widely recognized means to preserve autonomy and quality of life during aging (Wallace, 2005). Physically fit older adults have been shown to have lower blood pressures and higher cerebrovascular reserve (Bailey et al., 2013, Barnes et al., 2013, Bherer et al., 2013, Brown et al., 2010). Cross-sectional studies have suggested that regular exercise may be partly protective against cognitive decline (Brown and Thore, 2011, Brown et al., 2010, Churchill et al., 2002, Etnier et al., 2006, Kramer et al., 2006, Rogers et al., 1990, Yaffe et al., 2001).
It has been hypothesized that the effects of cardiorespiratory fitness on cognition may be partly mediated through preserved vascular health, because fitness has been shown to be associated with better health both at the level of large arteries (Arena et al., 2009, Binder et al., 2006, Tarumi et al., 2013) and cerebral microvessels (Bailey et al., 2013, Barnes et al., 2013, Brown et al., 2010). However, recent work suggests that the relationship between cardiorespiratory fitness and CVR may be more complex than previously thought. Thomas et al. (2013) have shown that older master athletes have lower BOLD CVR, but preserved baseline cerebral blood flow (CBF), as compared with age-matched older sedentary controls. Part of this complexity may arise from the method used to measure CVR, because arterial spin labeling (ASL), BOLD, and ultrasound are used in different studies. BOLD and ASL provide the advantage of spatial information and ASL of physiological specificity, because it is sensitive to flow rather than an ambiguous mixture of flow, volume, and metabolism, but it suffers from a low signal to noise ratio. Here, we have chosen to measure BOLD CVR to maximize sensitivity.
We have previously shown that some vascular and metabolic brain functions are impaired in healthy older adults as compared with young adults (Gauthier et al., 2013). Here, we further characterize age-related changes in aortic pulse wave velocity (PWV), BOLD CVR, as well as cardiorespiratory fitness (VO2 max) and executive function within a group of younger and older adults. We further document the links between these parameters within the older group. We anticipate that younger adults will show higher executive function, measured as a lower reaction time on the modified Stroop task, lower aortic stiffness, higher cardiorespiratory fitness, and higher CVR than older adults. We further expect that within the older group, better performance on an age-sensitive cognitive task in healthy older adults is associated with greater aortic elasticity, higher cardiorespiratory fitness level, and higher BOLD CVR, in line with the hypothesis that preserved executive functions are partly the result of a healthy vasculature. In subsequent portions of this article, the acronym CVR should be taken to indicate BOLD CVR unless otherwise indicated.
Section snippets
Participants
Acquisitions were conducted in a cohort of 31 young (21 males, with mean age of 24 ± 3 years) and 54 older community-dwelling healthy participants (17 males, with mean age of 63 ± 5 years) on a Siemens TIM Trio 3T MRI system (Siemens Medical Solutions, Erlangen, Germany). All participants gave informed consent, and the project was approved by the Comité mixte d’éthique de la recherche du Regroupement Neuroimagerie/Québec.
Exclusion criteria for this study included significant claustrophobia,
Results
The health and cognitive characteristics of this cohort are summarized in Table 1. All participants were healthy and did not show signs of mild cognitive impairment. Descriptive statistics for the comparison of the young and older groups are shown in Table 2. Modified Stroop reaction time was higher on average within the older as compared with the young group (1247.90 ± 204.50 vs. 898.20 ± 211.10 ms, respectively, p = 2 × 10−10). Furthermore, the standard deviation of both groups was similar,
Discussion
The impact of vascular aging on cerebral health and cognition, as well as the modulating influence of cardiorespiratory fitness have recently been the subject of much research effort. With the aging of our population, it has become imperative to determine the key factors that help maintain quality of life in later years. Here, we demonstrate within a single cohort of healthy younger and older adults the age-related decline in executive function, aortic elasticity, cardiorespiratory fitness and
Conclusion
In summary, this study reports age-related decline changes in executive function, aortic elasticity, and cardiorespiratory fitness within a single group of healthy younger and older adults. Furthermore, this study demonstrates a link between vascular health, as expressed in the aorta, with executive function on a modified Stroop task. We also report a positive association between aerobic fitness and executive function. This link between fitness and executive function may be mediated through
Disclosure statement
The authors have no conflicts of interest to disclose.
Acknowledgements
The authors thank Carollyn Hurst and André Cyr for their help with data acquisition, Élie Mousseaux, Alban Redheuil, and Alain Herment for their help with the aortic protocol, Mélanie Renaud and Élodie Boudes for their help with logistics, and Christopher Steele for helpful discussions. They thank Céline Denicourt for performing the blood draws. They thank Jiongjiong Wang of the Department of Neurology at UCLA who provided the dual-echo pseudo-continuous arterial spin labeling sequence. This
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