Extracranial Carotid Artery Stenosis: The Effects on Brain and Cognition with a Focus on Resting‐State Functional Connectivity

Abstract

Extracranial carotid artery stenosis (ECAS) due to the presence of atherosclerotic plaque is a well-known risk factor for stroke. Several structural imaging studies have investigated the effect of ECAS on the brain, focusing on structural damage (in particular cerebral small vessel disease) and on the rearrangement of the cerebral circulation. For example, it is known from the literature an association between carotid stenosis and cerebral small vessel disease, and it is also noted that a series of compensatory mechanisms are activated by the cerebrovascular system in order to overcome the cerebral hypoperfusion that is induced by the ECAS. Several neurocognitive studies have also investigated the association of ECAS with cognitive deficits. While the evidence tends to favor a direct association between ECAS and cognition, the actual relationship remains controversial. In the last decade, various resting-state functional connectivity (rs-fc) magnetic resonance (MR) studies have tried to elucidate the "in vivo" mechanisms underlying the cognitive impairment observed in these patients. Although these studies have been performed on small cohorts of patients without standardized protocols, it is plausible that in the future, such studies will help find early stage markers of cognitive impairment. This could permit an extension of indications for revascularization for the treatment of cognitive impairment in selected patients. The aim of this narrative review is to discuss the current knowledge on the effects of ECAS on brain and cognition by analyzing the main evidence from animal and clinical studies, with a special focus on rs-fc MR studies.

Disrupted Topological Organization of Functional Networks in Asymptomatic Carotid Plaque Without Significant Carotid Stenosis: A Resting-State fMRI Study

“…Carotid plaque and carotid stenosis reflect different stages of carotid atherosclerosis. A recent review of the effects of carotid stenosis on the brain and cognition (Porcu et al, 2020) summarized the disrupted functional connectivity and cognitive impairment in patients with carotid stenosis (Wang and Xiao, 2017;Gao et al, 2019). Many studies have reported that the cerebrovascular system activates a series of compensatory mechanisms to overcome the cerebral hypoperfusion that is induced by carotid stenosis (Shakur et al, 2014;Zarrinkoob et al, 2019).…”

“…Previous imaging studies have investigated the effects of carotid stenosis on the brain, focusing on structural damage and functional connectivity (Porcu et al, 2020). Asymptomatic carotid stenosis has been shown to have a detrimental effect on neuronal activity and regional functional connections (Rocque et al, 2012).…”

Impact of carotid stenosis on cerebral hemodynamic failure and cognitive impairment progression: a narrative review

“…Rao et al (36) compared the different neuropsychological approaches and found that findings were too contrasting and inhomogeneous to be correctly interpreted and compared. In general, the findings about this topic, underline an impact on general cognitive functions and some more involvement of memory, attention, and executive functions but without a specific domain compromise (34,36,54,61).…”

“…Recently, several studies showed, with the use of MRI or digital subtraction angiography, the relevance of collateral circles in preserving cognitive functions in patients with carotid stenosis (34). In the presence of a failure of the collateral vessels system, blood flow derangement occurs and it can induce a worsening of cerebral functions, including cognitive activities.…”

“…Also cerebral infarcts and microinfacts are associated with carotid stenosis, and all these entities are correlated with cognitive impairment (46). WMLs are related to a gliotic reaction due to chronic hypoperfusion while silent infarcts are the results of the occlusion of perforating arteries (34).…”