Asymptomatic carotid artery stenosis (ACS) is a common clinical vascular disorder and is frequently identified incidentally on screening evaluations. It has been recognized as a cause of cerebrovascular disease [1], [2], and its management is mainly based on the degree of stenosis [3]. In fact, ACS may not be clinically silent [4]. Cognitive impairment is one of the symptoms of ACS, and most studies have reported an association between ACS and cognitive impairment [5], [6]. Patients with ACS have been shown to perform worse on both the overall composite cognitive score and domain-specific neuropsychological tests of learning, working memory, attention and executive ability [7]. Even asymptomatic low-grade carotid artery stenosis has been associated with a greater decline in follow-up cognitive performance [8].

However, the pathophysiology of cognitive decline in ACS remains unclear. White-matter hyperintensities (WMHs) are one of the potential etiologies to explain this decline. WMHs are the most noticeable and easily accessible marker on T2-weighted magnetic resonance imaging (MRI) scans, and have been reported to show a higher prevalence in patients with slight-to-severe ACS [9]. However, some studies did not observe an association between carotid plaque severity and the progression of WMHs [8], [10], which is inconsistent with findings showing that cognitive decline is related to the degree of vascular stenosis. Thus, the role of WMHs in ACS-induced cognitive impairment and the potential underlying mechanisms remain unclear, and more granular analyses of WMHs may provide a deeper understanding of the underlying neuropathology and their effects [11]. Considering the critical role of the cholinergic pathway in the cognitive function and memory processes, we aimed to determine whether ACS-induced cognitive impairments were related to the cholinergic hyperintensity pathway.