Impact of pulse pressure on cerebrovascular events leading to age-related cognitive decline

Abstract

Aging is a modern concept: human life expectancy has more than doubled in less than 150 yr in Western countries. Longer life span, however, reveals age-related diseases, including cerebrovascular diseases. The vascular system is a prime target of aging: the "wear and tear" of large elastic arteries exposed to a lifelong pulsatile pressure causes arterial stiffening by fragmentation of elastin fibers and replacement by stiffer collagen. This arterial stiffening increases in return the amplitude of the pulse pressure (PP), its wave penetrating deeper into the microcirculation of low-resistance, high-flow organs such as the brain. Several studies have associated peripheral arterial stiffness responsible for the sustained increase in PP, with brain microvascular diseases such as cerebral small vessel disease, cortical gray matter thinning, white matter atrophy, and cognitive dysfunction in older individuals and prematurely in hypertensive and diabetic patients. The rarefaction of white matter is also associated with middle cerebral artery pulsatility that is strongly dependent on PP and artery stiffness. PP and brain damage are likely associated, but the sequence of mechanistic events has not been established. Elevated PP promotes endothelial dysfunction that may slowly develop in parallel with the accumulation of proinflammatory senescent cells and oxidative stress, generating cerebrovascular damage and remodeling, as well as brain structural changes. Here, we review data suggesting that age-related increased peripheral artery stiffness may promote the penetration of a high PP to cerebral microvessels, likely causing functional, structural, metabolic, and hemodynamic alterations that could ultimately promote neuronal dysfunction and cognitive decline.

Cerebral and skeletal muscle feed artery vasoconstrictor responses in a mouse model with greater large elastic artery stiffness

“…The consequences of large elastic artery stiffening are becoming increasingly appreciated, as described in previous reviews (Mitchell, 2008;O'Rourke & Safar, 2005;Thorin-Trescases et al, 2018). In particular, mounting evidence suggests an association between greater large elastic artery stiffness and lower cerebral blood flow, in addition to cognitive impairment and Alzheimer's disease (Jefferson et al, 2018;Knutsen et al, 2018;Meyer et al, 2017;Mitchell et al, 2011;Oh et al, 2016;Pase et al, 2016;Tarumi et al, 2011).…”

“…Likewise, our previous studies in these mice found that greater large elastic artery stiffness led to impaired endothelium‐dependent dilatation in MCAs, but not GFAs (Walker et al., ). The reason for the apparent greater vulnerability of cerebral arteries to increased large elastic artery stiffness is unknown, but potential mediators might include the higher resting blood flow in the brain (Mitchell, ), the thinner arterial wall and lack of external elastic lamina in cerebral resistance arteries (Thorin‐Trescases et al., ; Walker et al., ), or the closeness to the heart, at least compared with skeletal muscle feed arteries in the leg. It is also important to consider the role of autoregulation by cerebral resistance arteries in maintaining constant cerebral blood flow (Mitchell, ).…”

“…Stiffening of the large elastic arteries (i.e. the aorta and carotid arteries) is a key feature of advancing age (Avolio et al, 1983) and is hypothesized to have detrimental effects on the small arteries and the microvasculature (Mitchell, 2008;Thorin-Trescases et al, 2018).…”

“…When stiffness of the large elastic arteries is increased, there is less dampening of the pulse by the central arteries, leading to greater pulsatility of blood flow and pressure in resistance arteries (Mitchell, 2008;Thorin-Trescases et al, 2018). This greater pulsatility in resistance arteries may lead to impaired arterial function (Mitchell, 2008;Thorin-Trescases et al, 2018).…”

A New Rat Model of Chronic Cerebral Hypoperfusion Resulting in Early-Stage Vascular Cognitive Impairment

“…Furthermore, in this experiment, we explored the differences between the BCAS and BCAO models and tried to explain these differences with respect to microcirculatory dysfunction. Cerebral microcirculatory dysfunction is one of the common pathologies associated with vascular cognitive impairment (De Silva and Faraci, 2016), which causes changes in white matter lesions (Iadecola et al, 2019) and cognitive dysfunction (Thorin-Trescases et al, 2018). For example, Kitamura et al used spontaneously hypertensive rats as a model of early-stage cerebral small vessel disease.…”