Cerebral vascular reactivity and cognitive performance in patients with extracranial asymptomatic carotid stenosis

Background: Preliminary studies have reported cognitive dysfunction in unilateral asymptomatic carotid stenosis (ACS). Impaired cerebral hemodynamic status measured by cerebrovascular reactivity has been associated with cognitive dysfunction in unilateral ACS. Aims: (1) To evaluate cognitive performance in bilateral ACS compared to unilateral ACS and healthy subjects and (2) to explore the relationship between cognitive performance and cerebral hemodynamic status in bilateral ACS. Methods: Asymptomatic patients with ultrasound evidence of bilateral or unilateral ACS (60 %-99 % diameter reduction) were prospectively collected. Healthy subjects (HS) comparable for demographics and vascular risk profile served as controls. A neuropsychological investigation included phonemic and categorical Verbal Fluency (VF) tests to explore the left hemisphere and Colored Progressive Matrices (CPM), and Complex Figure Test Copy (CFTC) tests to explore the right hemisphere. Cerebrovascular reactivity (CVR) to hypercapnia using the transcranial Doppler (TCD) based breath-holding index (BHI) test was performed in each subject. Impaired CVR was defined as a BHI\0.69. Generalized linear multivariate and univariate models were employed to evaluate the mean difference on left and right cognitive test abilities in bilateral ACS patients with left and right preserved or impaired CVR. Vascular risk factors, education years, mini-mental status examination (MMSE), and current medications were included as covariates. Results: 333 consecutive subjects were included: 126 bilateral ACS; 73/75 left/right unilateral ACS; 56 HS; mean age: 70 ± 3.78 years; males: 65 %; education years: 10.3 ± 3.7; MMSE score: 26.7 ± 1.27. Bilateral and unilateral ACS patients showed significantly lower scores in all cognitive tests compared to HS (p\0.05). In the multivariate analysis, among bilateral ACS an impaired CVR in the right side was associated with a significantly reduced CPM score: from an estimated mean of 32.6 [95 % Confidence Interval (CI): 29.8–35.4) to 23.0 (95 % CI: 20.2–25.8) and the CFTC score from 34.7 (95 % CI: 32.0–37.4) to 26.0 (95 % CI: 23.3–28.7). Similarly, an impaired CVR on the left side was associated with a reduced phonemic VF score: 13.5 (95 % CI: 11.2–15.8) to 7.5 (95 % CI: 5.4–9.7) and categorical VF score from 21.1 (95 % CI: 18.1–24.1) to 12.3 (95 % CI: 9.5–15.1). All comparisons were statistically significant (p\0.05). Conclusions: Patients with unilateral or bilateral ACS are more likely to suffer cognitive dysfunction compared to healthy controls. Impaired CVR predicts the development of cognitive dysfunction in bilateral ACS. A non-invasive assessment of CVR using the TCDbased BHI test may contribute to a more comprehensive risk stratification in these patients.