Arterial stiffness, cognitive impairment and dementia: confounding factor or real risk?

Abstract

Large artery stiffness is a frequent condition that arises with ageing, and is accelerated by the presence of co-morbidities like hypertension, obesity and diabetes. Although epidemiological studies have indicated an association between arterial stiffness, cognitive impairment and dementia, the precise effects of stiff arteries on the brain remains obscure. This is because, in humans, arterial stiffness is often accompanied by other factors such as age, high blood pressure, atherosclerosis and inflammation, which could themselves damage the brain independently of stiffness. Therefore, the question remains: is arterial stiffness a true risk for cognitive decline?Or, is it a confounding factor? In this review, we provide an overview of arterial stiffness and its impact on brain function based on human and animal studies. We summarize the evidence linking arterial stiffness to cognitive dysfunction and dementia, and discuss the role of new animal models to better understand the mechanisms by which arterial stiffness affects the brain. We close with an overview of treatments to correct stiffness and discuss the challenges to translate them to real patient care.

Sex moderates the relationship between aortic stiffness, cognition and cerebrovascular reactivity in healthy older adults

“…Similarly, Waldstein et al reported males as scoring significantly lower than females on tests of verbal memory at higher levels of pulse pressure, an alternative measure of arterial stiffness (Waldstein et al 2008) . In addition, there is good agreement in the literature showing that arterial stiffness and related central hemodynamics are associated with reductions in cognitive performance on memory, processing speed, and executive function tasks (Iulita et al 2018;Singer et al 2014; . However, these studies are limited because they have used a nonspecific measure of cognition (i.e MMSE).…”

“…It is well established that elevated AS is an independent predictor of CVD (Mitchell 2009) . The elasticity of large arteries allows for the dampening of the arterial pressure waveform, transforming the pulsatile flow at the heart level into steady blood flow into the micro-vessels (Scuteri et al 2011;Iulita et al 2018;. Unfortunately, during aging, large arteries (e.g the aorta, the carotids etc) become stiffer and show a reduced capacity to dampen the arterial pressure waveform .…”

“…Thus, this raises the possibility that a portion of the sex effects observed in the literature could be mediated, in part, by differences in HGB levels. AS is also associated with downstream organ damage, especially in high-flow organs such as the brain Iulita et al 2018;Mitchell 2009;O'Rourke and Safar 2005; . Indeed, high pulsatile flow following AS may damage cerebral microvessels, thus, leading progressively to changes in cerebral blood flow (CBF) (Singer et al 2013;Tarumi et al 2013;Tarumi et al 2011) .…”

The many faces of vascular cognitive impairment

“…In the review article by Dr. Iulita, Dr. Girouard and coworkers of this edition, arterial stiffness constitutes the main topic and the authors introduce a new mouse model that allows the study of the specific effects of arterial stiffness as an isolated parameter, on brain's health, and discusses in detail diverse pharmacological interventions targeting the vasculature (Iulita et al . ). While no effective pharmacological agents are yet available for neither Alzheimer's disease nor vascular cognitive impairment, a large proportion of research focuses on non‐pharmacological interventions.…”

“…Today, knowing the role of multiple parameters such as oxidative stress, inflammation, bloodbrain barrier permeability, amyloid accumulation, cerebrovascular dysfunctions and white matter lesions in the pathogenesis of vascular dementia, research is oriented toward multitarget drugs (Leon and Marco-Contelles 2011;Perez et al 2015). In the review article by Dr. Iulita, Dr. Girouard and coworkers of this edition, arterial stiffness constitutes the main topic and the authors introduce a new mouse model that allows the study of the specific effects of arterial stiffness as an isolated parameter, on brain's health, and discusses in detail diverse pharmacological interventions targeting the vasculature (Iulita et al 2018). While no effective pharmacological agents are yet available for neither Alzheimer's disease nor vascular cognitive impairment, a large proportion of research focuses on non-pharmacological interventions.…”