Examining the Effects of Lateralized Carotid Stenosis and Post-Procedural Microembolism on Cognitive Performance and Outcome Evaluations Following Revascularization

Background: Carotid artery stenosis is an important risk factor of ischemic stroke. However, the role of carotid artery stenosis in cognitive deficits remains controversial. In our existing project, we elected a model of timed cognition in an attempt to tackle the limitations of commonly used neuropsychological tests, and to address the relationship between cerebral hypoperfusion and cognitive processing speed. Our preliminary data suggest that the occurrences of procedural-related ischemic lesions and the laterality of carotid stenosis seem to play important roles in moderating the effects of carotid stenosis and carotid angioplasty and stenting (CAS) on cognitive changes. Aims: The general purposes of this proposed project intend to extend the scope our existing project to examine the effects of the patient-related (laterality) and procedure-related (peri-CAS lesions) factors on the relationships between carotid artery stenosis, CAS, and cognitive functions. Methods: A series of studies will be carried out to (a) validate the alternative forms of the tests and test the applicability of these forms; (b) test if the occurrences of peri-CAS lesions can lead to cognitive deficits and impede the beneficial effects of CAS on cognitive functions; (c) to examine the role of unilateral carotid stenosis in moderating the effects on the cognitive changes produced by CAS. The research protocols and data analyses of the studies will be based on between-group or mixed factorial designs. In this 3-year project, thirty volunteers (aged 18-30 years) and 50 older volunteers (aged 50-75 years) will be recruited. They will serve as reference groups for deriving measures of cognitive speed and validating the alternative forms of the tests used in the proposed project. We also intend to recruit 160 participants with different grades of carotid stenosis from a stroke unit. They will be allocated to three different groups: the revascularization group (n = 80), the medication group (n = 40) and the control group (n = 40) based on their severity of stenosis and choice of treatments. All participants will undergo three phases of neuropsychological assessment, baseline (pre-CAS), 1 month, and 6 months after CAS or medications. The revascularization group will undergo diffusion weighted magnetic resonance image (DWI) in 3 phases (pre-CAS, 1 week and 6 months after CAS) for identifying and verifying new peri-CAS lesions. The revascularization group will be divided into two subgroups based on the presence or absence of new ischemic lesions on DWI performed at 1 week after CAS. The testing data accumulated throughout the project will be analyzed by MANOVA or MANCOVA where appropriate. The change scores across each phase will be used to derive reliable change index and/or multiple regression equations based on the medication and control groups. The number of cases falling in the ‘significant change’ range will be calculated and analyzed by 2 tests to examine the group differences (with lesions versus without) according to specific cognitive domains. To address the laterality effects, patients with significant stenosis will be further regrouped based on the side of stenosis and operated carotid (left versus right). Thus, laterality  treatment will be used as independent variables, and the testing data will be analyzed by the same methods described above. Expected outcomes: We expect the presence of peri-CAS lesions may result in cognitive impairments, which may further impede the beneficial effects of CAS on cognitive changes. We also anticipate that the difference in the sidedness of carotid stenosis may reveal different levels of performance on different cognitive domains that are predominantly regulated by the left and right hemisphere, respectively. In addition, depending on which side of CAS is treated, we should expect to see more cognitive improvement in the performance corresponding to the hemispheric functions in effect than that of its counterpart.

Project ID:PF10008-0885
External Project ID:NSC100-2410-H182-008-MY2