Biomedical Research

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- Biomedical Research (2016) Volume 27, Issue 2

Cognitive outcome after carotid artery stenting in patients with cerebral ischemia.

Wei Yue1,2#, Zhihong Shi1,2#, Miao Zhang1,2, Shuai Liu, RN1,2, ShuLing Liu, RN1,2, Ting Zhang1,2, Xiaoguang Tong1,3, Yuying Zhou1,2, Yong Ji1,2*
1Tianjin Key Laboratory of Cerebrovascular and of neurodegenerative diseases, PR. China
2Department of neurology, Tianjin Huanhu Hospital, Tianjin, PR. China
3Department of neurosurgery, Tianjin Huanhu Hospital, Tianjin, PR. China
#Wei Yue and Zhihong Shi contributed equally to this work.
Corresponding Author:Yong Ji, Tianjin Huanhu Hospital, Qixiangtai, Tianjin, PR. China.
Accepted: November 26, 2015
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Background: Chronic cerebral hypoperfusion may lead to cognitive decline in patients with chronic stenosis or occlusion of the cervicocerebral vessels, and the effects of stent placement on neurocognitive function have been controversial.

Methods: A series of 105 patients, who were identified with arterial stenosis or occlusion and abnormal cerebral perfusion in the area of the stenotic vessel based on computed tomography (CT) angiography or magnetic resonance angiography (MRA) and magnetic resonance (MR) or CT perfusion were selected to investigate. A battery of neuropsychological tests, including the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA), were assessed 1 week before and 90 days after the cervicocerebral vessel stenting, or conventional angiography without intervention.

Results: Patients were subdivided into 2 groups (n=83 carotid artery stents [CAS]); no intervention (n=22) serving as a control group. Significant improvements in MMSE (CAS 23.9 [4.9] vs 25.4 [4.7] for before vs after the procedures; P<0.01) and in MoCA (CAS 19.9 [6.4] vs 22.0 [6.0] for before vs after the procedures; P<0.01) were observed in the intervention groups. Orientation, delayed recall and abstraction were also improved.

Conclusions: Successful cervicocerebral vessel stenting improve cognitive function in patients with cervicocerebral vessels stenosis or occlusion with a corresponding perfusion abnormality.


Arterial stenosis, Carotid stenting, Brain perfusion, Neurocognitive function.


Impaired cognitive function is often reported in patients with carotid artery stenosis or occlusion. As is known to all, there is an independent risk factor for the progression of mild cognitive impairment (MCI) to dementia which is carotid stenosis [1,2,3]. Cerebral emboli and hypoperfusion which play key roles in this process can be improved by angioplasty [4,5]. Most of the studies that have evaluated cognitive functions before and after carotid endarterectomy (CEA) or carotid artery stenting (CAS) have reported either improvement or no change in cognition [6-13].
The purpose of this study is to investigate the effect of CAS on neurocognitive function in patients with stenosis or occlusion of the cervicocerebral vessels and objective hypoperfusion.

Materials and Methods

A total of 105 patients aged 40 to 80 years with carotid artery stenosis or occlusion were consecutively selected from the Department of cerebral vascular Neurosurgery, Huanhu Hospital, Tianjin, China from March 2011 to December 2011. All patients had persistent neurologic symptoms, including transient ischemic attacks, dizziness or stroke. The score of modified Rankin Scale was 0-2. Cervicocerebral vessel stenosis or occlusion was documented by computed tomography angiography (CTA) or magnetic resonance angiogram (MRA). Objective perfusion abnormalities corresponding to the area of the stenotic or occluded vessel were documented by magnetic resonance (MR) perfusion; except for 10 patients who were evaluated by CT perfusion because of a contraindication to magnetic resonance imaging. All of the excluded patients presented an ischemic stroke in previous 14 days, catheter-based techniques, arteriovenous malformation, or aneurysm, history of previous bleeding disorder, plan to carry out any operation within 1 month, life expectancy is less than 1 year, aphasia, right-sided hemiparesis, marked depression or a mental disorder, who were unable to comply with the study assessment or with a concomitant cognitive impairment, including Alzheimer’s disease and other dementia related to degenerative disease Table 1.
Treatment process
We use baseline CTA or MRA to assess the presence of vascular stenosis or occlusion, which allowed risk stratification before conventional angiography.
We use the North American Symptomatic Carotid Endarterectomy Trial (NASCET) for cervical carotid lesions and the Warfarin and Aspirin Symptomatic Intracranial Disease (WASID) criteria for evaluation of the stenotic vessels using conventional angiograms before and after endovascular treatment [14,15].
Pretreatment of aspirin and clopidrogel were taken to all participants for more than 5 days if they were not already taking these medications. Technical success was defined as a less than 30% residual stenosis after the stent implantation; while, in patients with a stenosis more than 90%, the residual stenosis was extended to approximately 60% in order to reduce the risk of hyperperfusion syndrome postoperatively [16]. During CAS, distal protection devices were used to avoid distal cerebral emboli.
Brain perfusion follow up
Magnetic resonance or CT imaging perfusion data were analyzed on an advanced workstation (SyngoMMWP VE27A, SIEMENS; Advantage 4.2, GE Healthcare). Cerebral blood volume (CBV), cerebral blood flow (CBF), time to peak (TTP) and mean transit time (MTT) were calculated. We divided the brain perfusion into three levels by using a qualitative grading system: 0, the perfusion situation is normal and complete; 1, hypoperfusion were presented by low CBF, delayed TTP, increased MTT, decreased flow, but the CBV is still normal or elevated; or 2, hypoperfusion with declined CBV. At least one level decline of the grading system is considered to be an improvement in perfusion after recanalization [17].
Neurocognitive function evaluation
A series of cognitive tests were assessed in the week before and 120 days after the intervention or conventional angiogram without intervention. A cognitive function evaluation was performed by an independent clinical neurologist, who was blinded to the outcome of the intervention. Functional assessments, including activities of daily living (ADL) and the Barthel Index were used. Cognitive assessments that included the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) were used.
MMSE is one of the most influential screening tool for cognitive impairment currently; however it does not contain much capacity to test frontal/executive or visuospatial functions and abstraction. Also, MMSE is not sensitive to mild cognitive impairment [18,19]. In the evaluation of mild cognitive impairment, Montreal cognitive assessment (MoCA) scale as a simple and brief screening tool with high sensitivity for subtle cognitive impairment is superior to the MMSE scale [20-22]. Compared to MMSE, MoCA adds more frontal lobe testing items which reflect the visual space and executive function; it appears that MoCA could be recommended as more appropriate tool for the assessment of cognitive changes in patients with carotid stenosis.
Informed written consent was obtained from all subjects and their relatives. The medical ethics committee of Huanhu Hospital approved this study.

Statistical Analysis

Continuous data are presented as means (SD). Discrete data are presented as counts and percentages. Analysis of variance (ANOVA) was used to compare differences for continuous and normally distributed data, and Chi-square analyses were done for categorical data among the 2 groups (CAS and CTR). Significant main effects in ANOVA were followed up with two-tailed t-tests for post hoc pairwise comparisons. Paired continuous data were compared by the Wilcoxon signed rank sum test. Pearson's correlation coef ficients were used to assess the correlation between the change in brain perfusion and the changes in neuropsy chological test results. A two-sided P-value <0.05 was considered as a statistically significant difference. Statistical analyses were performed using SPSS 16.0 for Windows (SPSS, Inc., Chicago, IL, USA).


Technical success was achieved in all 105 patients. One patient with a left internal carotid artery occlusion (ICAO) were excluded, because of a small, nonfatal ipsilateral temporal lobe hemorrhage 2 days after successful CAS owing to the complication of right-sided hemiparesis. During the perioperative period, there were no neurologic or vascular complications noted in the remaining 104 patients. After 3 months follow-up, no patients had a new ischemic event according to independent neurologic examination.
Patients were subdivided into 2 groups as follows: CAS (n=83) and routine medical therapy with no intervention for arterial stenosis or occlusion (CTR or control group; n=22). Control group included 14 of them with carotid stenosis or occlusion, and 3 of them with middle artery stenosis or occlusion, and 5 of them with multiple artery stenosis or occlusion. All these control patients gave up stenting because of the potential risk of the interventions after conventional angiograms.
Patients’ baseline clinical characteristics and neurocognitive status were similar between the 2 groups. The preprocedural scores from ADL and the results of neuropsychological tests results were similar among 2 groups. The score of MoCA was between 9 and 28. However the score of MMSE was between 11 and 30, including 8 patients with normal score [5].
Table 2 shows neurocognitive scores at baseline and 90 days after the procedures in CAS. Significant improvements in MMSE (CAS 23.9 [4.9] vs 25.4 [4.7] for before and after the procedures; P<0.01), and MoCA (CAS 19.9 [6.4] vs 22.0 [6.0]; for before and after the procedures; P<0.01) were observed. In comparison, there were no significant changes in any test parameters at follow-up in the CTR group. The scores for orientation, delayed recall, abstraction, visuospatial and executive functions, attention and calculation were increased in the CAS group.


Our study suggests that patients harboring carotid artery stenosis or occlusion with a corresponding hypoperfusion derive a cognitive benefit from cerebral revascularization when properly selected for stenting. This study supports the theory that reversal of the hemodynamic disorder may reverse cognitive impairment.


In our series of patients, all showed a mild decline in cognition based on MoCA scores and had objective cerebral ischemia suggested from MR or CT hypoperfusion. But based on MMSE scores, 8 patients showed normal (30 score) before intervention. These results indicated MoCA is more sensitive than MMSE on subtle cognitive impairment related to vessel stenosis.
After 3 months of follow-up, CAS treatment group showed neurocognitive improvement according to MMSE and MoCA scores. Global cognitive improvements including orientation, delayed recall, abstraction, visuospatial and executive functions, attention and calculation were observed in the CAS group. This also suggests that MoCA is more suitable to assess the cognitive changes than MMSE, especially for the frontal function.
Several studies have confirmed cerebrovascular stenosis was associated with poorer cognitive performance [23-26]. Others have shown cognitive improvement in patients after carotid endarterectomy [27-30]. However, the effects of carotid stenting on cognitive outcome are controversial [31,32]. The main factor that may contribute to the diversity in cognitive responses is the detrimental effects of procedural emboli [33-36]. CAS can be widely used in high-risk patients with carotid stenosis because of the development of intervention materials and neuroimaging techniques, especially the distal protection device for cerebral embolism. The safety and effectiveness of CAS has been confirmed by clinical studies [37,38], and cognitive improvement after CAS has been reported in the several studies [6-13]. Our study also confirmed the safety and effectiveness of CAS. At 3 months follow-up, none of the CAS patients had a new ischemic event.
There were limitaions to this study. Some of the cases underwent CT perfusion (n=10) and most cases underwent MR perfusion (n=94). Most of the stenting cases did not have poststenting perfusion images. Finally, this study included a relatively small population of patients, with only 3 months of follow-up. The control patients were not selected randomized; most of them selected routine medical therapy because of the risk of stenting.


The project was supported by Tianjin Science and Technology Support Programs (Fundings Number: 12ZCZDSY02900 and 12ZCZDSY01600), Science and technology project of Tianjin Municipal Health Bureau( Funding Number: 11KG117) and Tianjin Natural Science Foundation(Funding Number: 13JCYBJC21300).

Tables at a glance

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