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Carotid stenosis constitutes a common vascular disease that significantly affects cerebral blood flow and thus is associated with patients' cognitive functions. Carotid revascularization techniques [carotid endarterectomy (CEA) and carotid artery stenting (CAS)] may benefit cognition, though there are opposing findings, reporting an apparent decrement in cognitive function, no effect, or an apparent improvement after revascularization. A great number of studies are trying to evaluate the effect of carotid revascularization (CEA, CAS) on patients' cognitive functions, as well as on their psychological condition and quality of life through a baseline and follow-up neuropsychological examination. Recent reviews refer only to the narrow limits of cognitive deficits that may be attributed to carotid stenosis, rather than elucidating the outfit of all aspects of mental and cognitive correlations. Most of those findings depict controversy in current literature as far as the neuropsychological effects of carotid revascularization techniques are concerned, while clinical entities of "vascular dementia" and "vascular depression", as well as intercurrent vascular risk factors are also addressed. This might be taken into consideration, when determining the optimal therapeutic strategy for tackling carotid artery occlusive disease, while best practice clinical decisions should be still focused on stroke prevention and symptoms alleviation, until further research on the field of neuroangiology presents undisputable conclusions regarding the underlying effects of revascularization on mood and cognition. Τhe neurovascular interface, as far as mental and neurocognitive impact of carotid stenosis is concerned, also, comprises, the conceptual pathophysiological entity of "atheroinflammation", underscoring the association of vascular lesions with cognitive impairment, major depressive disorder and bipolar disorder. Chronic recurrent ischemia and chronic low perfusion are also addressed from neurocognitive aspect, regarding therapeutic strategies that might be preferred so as to reduce the burden of chronic cerebrovascular disease in both symptomatic and asymptomatic patients, given the fact that inflammatory processes of vascular complexion underlie both neuroinflammation and atherosclerosis, affecting cerebral perfusion as well as cortical blood flow.

Background: Cardiovascular disease (CVD) is a major global health issue, primarily caused by atherosclerosis. Psychological factors may play a role in the development and progression of CVD. However, the relationship between psychological factors and atherosclerosis is complex and poorly understood. This study, therefore, aimed to examine the association of psychological factors with (i) coronary and carotid atherosclerosis and (ii) cardiovascular health according to Life's Essential 8, in a large Swedish cohort., Methods: This study utilized data from the Swedish CArdioPulmonary bioImage Study (SCAPIS), a large population-based project including individuals aged 50 to 65 years. Several psychological factors were analysed: general stress, stress at work, financial stress, major adverse life events, locus of control, feeling depressed, and depression. Coronary atherosclerosis was assessed as the degree of stenosis by coronary computed tomography angiography (CCTA) and coronary artery calcification (CAC) scores. Carotid atherosclerosis was examined using ultrasound. In addition, cardiovascular health was examined using the Life's Essential 8 concept created by the American Heart Association, which includes four health behaviors and four health factors. Associations were examined through binomial logistic regression (atherosclerosis variables) and linear regression (Life's Essential 8)., Results: A total of 25,658 participants were included in the study. The presence of financial stress, higher locus of control, and depression was weakly associated with increased odds of CCTA stenosis, CAC ≥ 1 and the presence of carotid plaques (all odds ratios: 1.10-1.21, 95% CI: 1.02-1.32) after adjusting for sex, age, and study site. However, these associations were attenuated and not statistically significant after additional adjustments for socioeconomic factors and health behaviors. Conversely, we observed inverse associations between the worst category for all psychological factors and cardiovascular health according to Life's Essential 8 score (all standardized β-Coefficient ≤-0.033, p < 0.001)., Conclusion: While there were no strong and consistent associations between psychological factors and atherosclerosis, the consistent associations of psychological factors with cardiovascular health by Life's Essential 8 may have relevance for future CVD risk. However, further studies are needed to elucidate the long-term effects of psychological factors on atherosclerosis development and cardiovascular health., (© 2024. The Author(s).)

Background: The association between carotid plaque and cognitive decline has recently been reported. However, the current research evidence is insufficient, and the possible causes of cognitive changes are unknown., Objective: This study aims to explore the relationships between carotid plaque and cognition functions, cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers in cognitively intact adults, and try to study the underlying mechanisms., Methods: We enrolled 165 cognitively normal participants from the Chinese Alzheimer's Biomarker and LifestylE (CABLE) study, who had CSF AD biomarker measurements and carotid ultrasound. Linear modeling was used to assess the association of carotid plaque with CSF biomarkers and cognition. Additionally, mediation analysis was conducted through 10,000 bootstrapped iterations to explore potential links between carotid plaque, AD pathology, and cognition., Results: We found that carotid plaque exhibited significant correlations with Aβ42 (β = -1.173, p = 0.022), Aβ42/Aβ40 (β = -0.092, p < 0.001), P-tau/Aβ42 (β = 0.110, p = 0.045), and T-tau/Aβ42 (β = 0.451, p = 0.010). A significant correlation between carotid plaque and cognition decline was also found in men (β = -0.129, p = 0.021), and mediation analyses revealed that the effect of carotid plaque on cognitive function could be mediated by Aβ42/Aβ40 (proportion of mediation = 55.8%), P-tau/Aβ42 (proportion of mediation = 51.6%, p = 0.015) and T-tau/Aβ42 (proportion of mediation = 43.8%, p = 0.015) mediated., Conclusions: This study demonstrated the link between carotid plaque and CSF AD biomarkers in cognitively intact adults, and the important role that AD pathology may play in the correlation between carotid plaque and cognitive changes.

Introduction: Common carotid intima-media thickness (cIMT) is a marker of subclinical atherosclerosis and is associated with cognitive decline. Although carotid atherosclerosis is more frequent in White than in Black participants, little is known whether race modifies the association between cIMT and cognitive decline., Methods: In this longitudinal analysis of the ELSA-Brasil, we assessed cIMT using ultrasound and cognitive performance using different domain tests. We used linear mixed models, interaction analysis, and race stratified analyses., Results: Baseline high IMT values were associated with memory (p < 0.001), verbal fluency (p < 0.001), TMT-B (p < 0.001)), and global cognitive decline (p < 0.001). Race was an effect modifier in the association between IMT and global cognitive decline (0.043), with stronger association in White (p < 0.001) than in Black (p = 0.009) participants., Discussion: Baseline IMT was associated with global and domain-specific cognitive decline and race modified this relationship, with stronger associations in White participants., Highlights: Carotid intima-media thickness (cIMT) was associated with cognitive decline. cIMT and cognitive decline association was stronger in White than in Black participants. We used inverse probability weighting to address attrition bias., (© 2023 the Alzheimer's Association.)

Background: Previous research from our group found that recent depressive symptoms were associated with 3-year change in carotid intima-media thickness (CA-IMT), a biomarker of cardiovascular disease risk, in an initially healthy sample of older adults. Trait measures of anxiety, anger, and hostility did not predict 3-year CA-IMT progression in that report., Purpose: The current study sought to reexamine these associations at a 6-year follow-up point., Methods: Two-hundred seventy-eight participants (151 males, mean age = 60.68 years) from the original sample completed an additional IMT reading 6 years following the initial baseline assessment., Results: Though not significant at 3-years, trait-anger emerged as a predictor of IMT progression at the 6-year point. When examined in separate regression models, both depression and trait-anger (but not anxiety or hostility) predicted 6-year IMT change (b = .017, p = .002; b = .029, p = .01, respectively). When examined concurrently, both depression and anger were independently associated with 6-year IMT progression (b = .016, p = .010, b = .028, p = .022, respectively). Exploratory analyses suggest that the relative contributions of anger and depression may differ for males and females., Conclusions: The use of sequential follow-ups is relatively unique in this literature, and our results suggest a need for further research on the timing and duration of psychosocial risk exposures in early stages of cardiovascular disease., (© Society of Behavioral Medicine 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The combined effects of increased life expectancy and the considerable number of persons reaching old age will magnify the dementia epidemic in the USA. Demonstration that subclinical atherosclerosis precedes and is associated with cognitive impairment suggests a modifiable risk factor for age-associated cognitive impairment and dementia. The purpose of this study is to determine whether subclinical atherosclerosis as measured by carotid artery intima-media thickness (CIMT) is associated with changes in cognitive function over time in older adults., Methods: This study combined longitudinal data from three clinical trials conducted between 2000 and 2013: the B-Vitamin Atherosclerosis Intervention Trial (BVAIT), the Women's Isoflavone Soy Health (WISH) trial, and the Early versus Late Intervention Trial with Estradiol (ELITE). Participants were recruited from the general population in the Greater Los Angeles area and were free of cardiovascular disease and diabetes; no cognitive or psychiatric exclusion criteria were specified. The same standardized protocol for ultrasound image acquisition and measurement of CIMT was used in all trials. CIMT measurements performed at baseline and 2.5 years were used in these analyses. Cognitive function was assessed at baseline and 2.5 years using a battery of 14 standardized cognitive tests. All clinical trials were conducted at the University of Southern California Atherosclerosis Research Unit, Los Angeles, and had at least 2.5 years of cognitive follow-up., Results: A total of 308 men and 1187 women, mean age of 61 years, were included in the combined longitudinal dataset for the primary analysis. No associations were found between CIMT and cognitive function at baseline or at 2.5 years. There was a weak inverse association between CIMT measured at baseline and change in global cognition assessed over 2.5 years (β (SE) = - 0.056 (0.028) units per 0.1 mm CIMT, 95% CI - 0.110, - 0.001, p = 0.046). No associations between CIMT at baseline and changes in executive function, verbal memory, or visual memory were found., Conclusions: In this sample of healthy older adults, our findings suggest an association between subclinical atherosclerosis and change in global cognitive function over 2.5 years. Stronger associations were observed longitudinally over 2.5 years than cross-sectionally. When analysis was stratified by age group (<65 and ≥65 years old), the inverse association remained statistically significant for participants in the older age group. Subclinical atherosclerosis of the carotid artery may be a modifiable correlate of cognitive decline in middle and older age., Trial Registration: BVAIT, NCT00114400 . WISH, NCT00118846 . ELITE, NCT00114517 ., (© 2022. The Author(s).)

Background Sexual assault is a risk factor for poor mental health, yet its relationship to cardiovascular disease risk is not understood. We tested whether women with a sexual assault history had greater carotid atherosclerosis levels and progression over midlife. Methods and Results A total of 169 non-smoking, cardiovascular disease-free women aged 40 to 60 years were assessed twice over 5 years. At each point, women completed questionnaires, physical measures, phlebotomy, and carotid ultrasounds. Associations between sexual assault and carotid plaque level (score 0, 1, ≥2) and progression (score change) were assessed in multinomial logistic and linear regression models, adjusted for age, race/ethnicity, education, body mass index, blood pressure, lipids, insulin resistance, and additionally depression/post-traumatic stress symptoms; 28% of the women reported a sexual assault history. Relative to non-exposed women, women with a sexual assault history had an over 4-fold odds of a plaque score of ≥2 at baseline (≥2, odds ratio [OR] [95% CI]=4.35 [1.48-12.79], P =0.008; 1, OR [95% CI]=0.49 [0.12-1.97], P =0.32, versus no plaque; multivariable); and an over 3-fold odds of plaque ≥2 at follow-up (≥2, OR [95% CI]=3.65 [1.40-9.51], P =0.008; 1, OR [95% CI]=1.52 [0.46-4.99], P =0.49, versus no plaque; multivariable). Women with a sexual assault history also had an over 3-folds greater odds of a plaque score progression of ≥2 (OR [95% CI]=3.48[1.11-10.93], P =0.033, multivariable). Neither depression nor post-traumatic symptoms were related to plaque. Conclusions Sexual assault is associated with greater carotid atherosclerosis level and progression over midlife. Associations were not explained by standard cardiovascular disease risk factors. Future work should consider whether sexual assault prevention reduces women's cardiovascular disease risk.

Background Emotional disorders are risk factors for atherosclerosis and consequent cardiovascular disease. However, it is not clear whether emotional symptoms (ESs) have direct effects on cardiovascular disease. The aim of the present study is to investigate the effects of early ESs on carotid atherosclerosis in young adults. Methods and Results We tested the association between expression of ESs at 11 and 15 years of age and carotid intima-media thickness at 18 years of age in the 1993 Pelotas Birth Cohort (N=5249, n=4336 with complete mental health data). ES s were assessed using the Strengths and Difficulties Questionnaire. Propensity score weighting procedure was run using generalized boosted regression model to adjust for potential confounding between exposure and outcome. We also tested whether traditional cardiovascular risk factors could mediate this relationship. Adjusted high expression of ESs , both at 11 and 15 years of age, led to mean increases in carotid intima-media thickness of 1.84 and 2.58 μm, respectively, at 18 years of age (both P<0.001). Longitudinal effects of ESs on atherosclerosis were direct and not significantly mediated by traditional cardiovascular risk factors. Male sex at age 15 years significantly enhanced the effects of ESs on carotid intima-media thickness at age 18 years ( P<0.001 for interaction): although high expression of ESs led to mean increases of 1.14 μm in females ( P<0.05), it led to mean increases of 5.83 μm in males ( P<0.001). Conclusions In this large birth cohort, expression of ESs in adolescence was longitudinally associated with a higher carotid intima-media thickness in young adults. The association is direct and not mediated by traditional cardiovascular risk factors. Interactions by sex might have important implications for designing future interventions.

Background: Studies on the relationship between carotid atherosclerosis and cognitive function in subjects from the general population are few and results have been inconsistent., Objective: We aimed to investigate the association between carotid atherosclerotic burden and cognitive function in a cross-sectional analysis of a population-based cohort aged 63-65 years., Methods: All habitants born in 1950 from Akershus County, Norway were invited to participate. A linear regression model was used to assess the association between carotid atherosclerosis and cognitive function. We used carotid plaque score as a measure of carotid atherosclerotic burden and the Montreal Cognitive Assessment (MoCA) for global cognitive function., Results: We analyzed 3,413 individuals aged 63-65 with mean MoCA score 25.3±2.9 and 87% visible carotid plaques. We found a negative correlation between carotid plaque score and MoCA score (r = -0.14, p < 0.001), but this association was lost in multivariable analysis. In contrast, diameter or area of the thickest plaque was independently associated with MoCA score. Lower educational level, male sex, current smoking, and diabetes were also associated with lower MoCA score in multivariable analysis., Conclusion: Carotid atherosclerotic burden was, unlike other measures of advanced carotid atherosclerosis, not independently associated with global cognitive function.

Objective: To examine the relationship between carotid atherosclerosis and cerebral cortical thickness and investigate whether cortical thickness mediates the association between carotid atheroma and relative cognitive decline., Methods: We assessed 554 community-dwelling subjects (male/female: 296/258) from the Lothian Birth Cohort 1936 who underwent brain magnetic resonance imaging and carotid Doppler ultrasound studies at age 73 years. The relationship between carotid atherosclerosis markers (internal carotid artery stenosis, intima-media thickness, velocity, pulsatility, and resistivity indexes) and vertex-wide cerebral cortical thickness was examined cross-sectionally, controlling for gender, extensive vascular risk factors (VRFs), and intelligence quotient at age 11 (IQ-11). We also determined the association between carotid stenosis and a composite measure of fluid intelligence at age 73 years. A mediation model was applied to examine whether cortical thickness mediated the relationship between carotid stenosis and cognitive function., Results: A widespread negative association was identified between carotid stenosis (median = 15%) and cerebral cortical thickness at age 73 years, independent of the side of carotid stenosis, other carotid measures, VRFs, and IQ-11. This association increased in an almost dose-response relationship from mild to severe degrees of carotid stenosis, across the anterior and posterior circulation territories. A negative association was also noted between carotid stenosis and fluid intelligence (standardized beta coefficient = -0.151, p = 0.001), which appeared partly (approximately 22%) mediated by carotid stenosis-related thinning of the cerebral cortex., Interpretation: The findings suggest that carotid stenosis represents a marker of processes that accelerate aging of the cerebral cortex and cognition that is in part independent of measurable VRFs. Cortical thinning within the anterior and posterior circulation territories partially mediated the relationship between carotid atheroma and fluid intelligence. Ann Neurol 2018;84:576-587., (© 2018 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.)

Objectives: Although the relationship between atherosclerosis and cognitive impairment has been studied and replicated, whether cognitive deficits in RA can be attributed to atherosclerotic changes is not well understood. This study investigated cognitive function in patients with RA and evaluated whether cognitive function was affected by carotid arterial atherosclerosis., Methods: We examined 70 RA patients and 40 healthy controls. RA activity was assessed by disease activity score with 28 joint-erythrocyte sedimentation rate (DAS28-ESR). Cognitive function was assessed by the Korean version of the Consortium to Establish a Registry for Alzheimer's disease (CERAD-K) neuropsychological battery. Carotid arteries were scanned for the presence of plaques and to assess intima-media thickness (IMT). We assessed potential risk factors of cognitive impairment in RA patients using regression analyses., Results: There was a significant difference between RA patients and healthy controls in the verbal fluency (p=0.004) and Boston naming test (p=0.035). Carotid ultrasound revealed significantly more plaque in RA patients than in healthy controls (p=0.017). RA patients with memory impairment had significantly higher DAS28-ESR scores (p<0.001), age (p=0.009), and mean cIMT (p=0.027) than RA patients without memory impairment. In multivariable regression analysis, CERAD-K total score showed a significant negative correlation with age (β=-0.415, p<0.001) or DAS28-ESR (β=-4.685, p<0.001), but no correlation was found between CERAD-K total score and presence of plaque or cIMT., Conclusions: Our results indicate that disease activity of RA and aging contribute to cognitive dysfunction, but there was no association between cognitive function and carotid atherosclerotic changes in RA patients.

Background and Aims: Arterial remodelling aims at normalising circumferential wall stress (CWS). Greater CWS in the carotid artery has previously been associated with the prevalence and severity of cerebral small vessel disease, a major cause of ageing-related cognitive decline. Here we test the hypothesis that greater carotid CWS is associated with poorer cognitive performance., Methods: We studied 722 individuals (60 ± 8 years, 55% men, 42.5% highly educated, blood pressure 137 ± 19/77 ± 11 mmHg, n = 197 with type 2 diabetes) who completed a neuropsychological assessment and underwent vascular ultrasound to measure the intima-media thickness (IMT) and interadventitial diameter (IAD) of the left common carotid artery at a plaque-free site. From IMT and IAD, lumen diameter (LD) was calculated. These structural measures were then combined with local carotid pulse pressure and brachial mean arterial pressure to obtain a measure of pulsatile (CWS pulsatile ) and average (CWS mean ) mechanical load on the vessel wall. Cognitive domains assessed were memory, executive function and attention, and processing speed., Results: After adjustment for age, sex, and education, regression analyses showed that neither CWS pulsatile nor CWS mean were associated with measures of cognitive performance (p-values ≥0.31). This null association did not differ by age or educational level, and was observed in both individuals with and without carotid plaque, diabetes and/or hypertension. In addition, none of the individual measures of carotid structure (i.e. IMT, IAD, and LD) was related to cognitive performance., Conclusions: The present cross-sectional study shows that carotid CWS is not associated with cognitive performance, at least not among relatively highly educated individuals in late middle age with adequately controlled cardiovascular risk factors., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

High-flow bypass followed by ligation of the internal carotid artery (ICA) is an effective treatment, but the impact of abrupt occlusion of the ICA is unpredictable, especially on postoperative cognitive function. The present study evaluated the clinical results as well as cognitive performances after high-flow bypass using radial artery graft (RAG) with supportive superficial temporal artery (STA)-middle cerebral artery (MCA) bypass, followed by ICA ligation. Ten consecutive patients underwent high-flow bypass surgery for large or giant ICA aneurysms of cavernous or cervical portion. Demographics, clinical information, magnetic resonance (MR) imaging, computed tomography, digital subtraction angiography (DSA), intraoperative somatosensory evoked potentials, neuropsychological examinations including the Wechsler Adult Intelligence Scale-Third Edition and the Wechsler Memory Scale-Revised (WMS-R), and follow-up data were analyzed. The aneurysm was located on the cavernous segment in eight cases and cervical segment in two cases, and mean aneurysm size was 27.9 mm. Postoperative DSA demonstrated robust bypass flow from the external carotid artery to MCA via the RAG, and no anterograde flow into the aneurysm. No patient showed new symptoms after the operation. Follow-up clinical study and MR imaging were performed in nine patients and showed no additional ischemic lesion compared with preoperative imaging. Seven patients completed neuropsychological examinations before and after surgery. All postoperative scores except WMS-R composite memory score slightly improved. High-flow bypass followed by ICA ligation can achieve good clinical outcomes. Successful high-flow bypass using RAG with supportive STA-MCA bypass and ICA ligation does not adversely affect postoperative cognitive function.

Aim: To clarify whether carotid atherosclerosis and its risk factors are associated with cognitive decline., Methods: We evaluated 206 individuals who visited our center for health screening. We carried out physical examinations, blood tests, intima-media thickness (IMT) measurement by carotid ultrasonography, brain magnetic resonance imaging scanning and cognitive function assessments. A total of 30 individuals, who had significant cerebrovascular lesions detected in magnetic resonance imaging scans, were excluded. To detect early cognitive decline, we defined "cognitive impairment (CI)" when a patient satisfied at least one of three criteria. These were Mini-Mental State Examination score <24, clock-drawing test score <4 coexisting with forgetfulness and Wechsler Memory Scale-revised delayed recall score below the normal range for the duration of education (>16 years of education: ≥9, 10-15 years: ≥5, 0-9 years: ≥3)., Results: Among 176 individuals, 27 were placed in the CI group. IMT was significantly higher in the CI group as compared with the non-CI group (mean ± SD: 2.0 ± 1.0 vs 1.7 ± 0.7, P = 0018 by Student's t-test). Other atherosclerotic risk factors, such as blood pressure, low-density lipoprotein cholesterol, and hemoglobin A1c, were not significantly different between the two groups. In multivariate analysis, maximum IMT was associated with impaired immediate recall score on Wechsler Memory Scale-revised, independent of the presence of deep white matter hyperintensities on the magnetic resonance imaging scan., Conclusions: Subclinical carotid atherosclerosis, defined as thickened IMT, could be a marker for early stages of CI, especially for immediate memory recall. The impairment is presumably caused by inducing cerebral microvascular dysfunction in the frontal lobe. Geriatr Gerontol Int 2018; 18: 65-71., (© 2017 Japan Geriatrics Society.)

Background: Violence against women has become a global public health threat. Data on the potential impact of exposure to violence on cardiovascular disease are scarce., Methods and Results: We evaluated the association between exposure to violence and subclinical cardiovascular disease in 634 disease-free women from the Mexican Teachers' Cohort who responded to violence-related items from the Life Stressor Checklist and underwent measures of carotid artery intima-media thickness in 2012 and 2013. We defined exposure to violence as having ever been exposed to physical and/or sexual violence. Intima-media thickness was log-transformed, and subclinical carotid atherosclerosis was defined as intima-media thickness ≥0.8 mm or plaque. We used multivariable linear and logistic regression models adjusted for several potential confounders. Mean age was 48.9±4.3 years. Close to 40% of women reported past exposure to violence. The lifetime prevalence of sexual violence was 7.1%, and prevalence of physical violence was 23.5% (7.7% reported both sexual and physical violence). Relative to women with no history of violence, exposure to violence was associated with higher intima-media thickness (adjusted mean percentage difference=2.4%; 95% confidence interval 0.5, 4.3) and subclinical atherosclerosis (adjusted odds ratio=1.60; 95% confidence interval 1.10, 2.32). The association was stronger for exposure to physical violence, especially by mugging or physical assault by a stranger (adjusted mean % difference=4.6%; 95% confidence interval 1.8, 7.5, and odds ratio of subclinical carotid atherosclerosis=2.06; 95% confidence interval 1.22, 3.49)., Conclusions: Exposure to violence, and in particular assault by a stranger, was strongly associated with subclinical cardiovascular disease in Mexican middle-aged women., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background and Purpose: Ultrasound markers of carotid atherosclerosis may be related to cognitive status. We hypothesized that individuals with greater carotid intima-media thickness (cIMT) and carotid plaque burden would exhibit worse cognition., Methods: One thousand one hundred sixty-six stroke-free participants from the NOMAS (Northern Manhattan Study) underwent carotid ultrasound and neuropsychological examination. Among them, 826 underwent a second neuropsychological examination an average of 5 years later. cIMT and plaque were assessed by a standardized B-mode ultrasound imaging and reading protocol. We used multivariable linear regression to examine cIMT, carotid plaque presence, and carotid plaque area as correlates of domain-specific neuropsychological Z scores cross-sectionally and over time. We also investigated possible effect modification by APOE ε4 allele, age, and race/ethnicity., Results: Participants had a mean (SD) age of 70 (9) years and were 60% women, 66% Hispanic, 15% white, and 18% black. Those with greater cIMT exhibited worse episodic memory after adjustment for demographics and vascular risk factors (β=-0.60; P =0.04). APOE ε4 carriers with greater cIMT exhibited worse episodic memory (β=-1.31; P =0.04), semantic memory (β=-1.45; P =0.01), and processing speed (β=-1.21; P =0.03). Participants with greater cIMT at baseline did not exhibit significantly greater cognitive decline after adjustment. APOE ε4 noncarriers with greater cIMT exhibited greater declines in executive function (β=-0.98; P =0.06). Carotid plaque burden was not significantly associated with cognition at baseline or over time., Conclusions: Subclinical carotid atherosclerosis was associated with worse cognition among those at higher risk for Alzheimer disease. Interventions targeting early stages of atherosclerosis may modify cognitive aging., (© 2017 The Authors.)

Anxiety is an affective disorder that is commonly observed after irreversible brain damage induced by cerebral ischemia and can delay the physical and cognitive recovery, which affects the quality of life of both the patient and family members. However, anxiety after ischemia has received less attention, and mechanisms underlying anxiety-like behaviours induced by chronic cerebral ischemia are under-investigated. In the present study, the chronic cerebral hypoperfusion model was established by the permanent occlusion of the bilateral common carotid arteries (two-vessel occlusion, 2VO) in rats, and anxiety-related behaviours were evaluated. Results indicated that 2VO induced obvious anxiety-like behaviours; the surface expressions of GABAB2 subunits were down-regulated; Brain derived neurotrophic factor (BDNF), tyrosine kinase B (TrkB) and neural cell adhesion molecule (NCAM) were reduced; Meanwhile, the surface expressions of G protein-activated inwardly rectifying potassium (GIRK, Kir3) channels were up-regulated in hippocampal CA1 in 2VO rats. Baclofen, a GABAB receptor agonist, significantly ameliorated the anxiety-like behaviours. It also improved the down-regulation of GABAB2 surface expressions, restored the levels of BDNF, TrkB and NCAM, and reversed the increased surface expressions of Kir3 in hippocampal CA1 in 2VO rats. However, the effects of baclofen were absent in shRNA-GABAB2 infected 2VO rats. These results suggested that activation of GABAB2 subunits could improve BDNF signalling and reverse Kir3 channel surface expressions in hippocampal CA1, which may alleviate the anxiety-like behaviours in rats with chronic cerebral hypoperfusion., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

We aimed to assess whether carotid siphon calcifications (as seen on computed tomography) are associated with worse performance in the Montreal Cognitive Assessment in 584 stroke-free individuals living in rural Ecuador. Using mean Montreal Cognitive Assessment score of subjects with Grade 1 calcifications (23.1 ± 4.2) as the referent category, fully adjusted generalized linear models showed significant associations between severity of carotid siphon calcifications and cognitive performance (mean Montreal Cognitive Assessment scores: 20.2 ± 4.8 for Grade 2 (p = 0.004), 19.7 ± 5.3 for Grade 3 (p = 0.0001), and 18.8 ± 4.1 for Grade 4 (p = 0.02)). Predictive Montreal Cognitive Assessment score margins were higher in individuals with Grade 1 calcifications than in other groups. This study shows an inverse relationship between calcium content in the carotid siphon and cognitive performance in Amerindians.

Background and Aims: Carotid artery intima-media thickness (CIMT) may be used as a biomarker for early cognitive impairment. However, the results of the association between CIMT and cognitive function in middle-aged subjects are mixed. We aimed to investigate this association in a large Brazilian sample with no history of stroke at baseline. Additionally, we tested the effect of interactions between CIMT and cardiovascular risk factors on cognitive performance., Methods: In this cross-sectional study, cognition was evaluated using the delayed word recall (DWRT), the category fluency, and the trail making tests (TMT). CIMT was measured at the common carotid artery. The association between CIMT and cognitive tests was investigated using linear regression models, adjusted for an extensive set of possible confounding variables. We also included interaction terms with selected risk factors., Results: The mean age of the 8208 participants was 49.6 ± 7.3 years, 44% were male, and 56% White. Increase in CIMT was associated with worse performance on the DWRT (β = -0.433, 95%CI = -0.724;-0.142, p = 0.004). We found effect modification of the association between cognitive function and CMIT by self-reported heart failure and alcohol intake. Participants had worse performance in the TMT if they had greater CIMT and current alcohol use (p < 0.0001). The interaction between CIMT and heart failure on TMT performance was not significant after adjustment for multiple comparisons (p = 0.07)., Conclusions: In this sample of middle-aged adults, CIMT was inversely associated with memory function. Additionally, the presence of alcohol use resulted in a stronger association of CIMT with worse performance on an executive function test., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: To compare the six-month outcome on mood, cognition and quality of life (QoL) in patients with severe carotid atherosclerosis (CA) who underwent carotid endarterectomy (CEA) with subjects who refused treatment., Methods: Cohort study on consecutive inpatients with CA (stenosis ≥ 50 %) (N = 46; age 72.56 ± 7.26; male 65.2 %). Intervention cohort: subjects who decided to undergo CEA (N = 35); Control cohort patients who refused CEA (N = 11). DSM-IV-Psychiatric diagnosis made by clinicians using interviews, QoL measured by Short Form Health Survey (SF-12); cognitive performance by WAIS Intelligent Coefficient (IC)., Results: The study showed a better improvement during six months in Overall IC, Performance IC and Verbal IC in the group that underwent CEA. QoL in the two cohorts did not reach statistical significance. Percentages of patients who improved in the CEA group were significantly higher with regard to Overall and Verbal IC scores, and at the limits of statistical significance in Performance IC. The differences of subject with improvement in SF-12 score in the two groups did not reach statistical significance. Ages below 68 were found to be determinant of a good outcome in Overall IC score. Limit: study conducted with a small sample size., Conclusions: Patients with severe carotid atherosclerosis who underwent CEA enhanced their cognitive performance.

Over the past decade a growing interest has been devoted to exploring the role of atherosclerosis in the development of dementia. Despite a well-known association between atherosclerosis risk factors in middle-life with later cognitive decline, the pathophysiological pathways underlying this association remain unclear. The current hypothesis is that neurodegenerative and vascular lesions coexist and have a synergistic role in the development of cognitive impairment and dementia. Carotid atherosclerosis (e.g. carotid plaques and intima-media thickness as measured by carotid ultrasonography) has been associated with cognitive decline and dementia and may help to better understand the complex interaction between the vascular and neurodegenerative processes. Furthermore, carotid atherosclerosis has been used in the recent field for dementia risk prediction. In this review, we discuss the physiopathological implications from the current available data on the relationship between carotid atherosclerosis and dementia as well as the interest of carotid biomarkers for individual dementia risk prediction.

Background and Purpose: The relationship between carotid artery intima-media thickness (IMT) and cognitive function in midlife remains relatively unexplored. We examined the association between IMT and cognitive function in a middle-aged epidemiological cohort of 2618 stroke-free participants., Methods: At the year 20 visit (our study baseline), participants from the Coronary Artery Risk Development in Young Adults study had IMT measured by ultrasound at the common carotid artery. Five years later, participants completed a cognitive battery consisting of the Rey Auditory-Verbal Learning Test of verbal memory, the Digit Symbol Substitution Test of processing speed, and the Stroop test of executive function. We transformed cognitive scores into standardized z scores, with negative values indicating worse performance., Results: Mean age at baseline was 45.3 years (SD, 3.6). Greater IMT (per 1 SD difference of 0.12 mm) was significantly associated with worse performance on all cognitive tests (z scores) in unadjusted linear regression models (verbal memory, -0.16; 95% confidence interval [CI], -0.20 to -0.13; processing speed, -0.23; 95% CI, -0.27 to -0.19; and executive function, -0.17; 95% CI, -0.20 to -0.13). In models adjusted for sociodemographics and vascular risk factors that lie earlier in the causal pathway, greater IMT remained negatively associated with processing speed (-0.06; 95% CI, -0.09 to -0.02; P, 0.003) and borderline associated with executive function (-0.03; 95% CI, -0.07 to 0.00; P, 0.07) but not with verbal memory., Conclusions: We observed an association between greater IMT and worse processing speed-a key component of cognitive functioning-at middle age above and beyond traditional vascular risk factors. Efforts targeted at preventing early stages of atherosclerosis may modify the course of cognitive aging., (© 2015 American Heart Association, Inc.)

Objectives: Stroke causes significant quality of life (QOL) deterioration and functional impairment. Carotid revascularisation by either endarterectomy (CEA) or stenting (CAS) is performed to prevent stroke. The direct effect of revascularisation on QOL is unclear. This study reviews (a) QOL after CEA, (b) QOL after CAS, (c) QOL differences between CEA and CAS, and (d) QOL compared with reference populations., Methods: Medline and Embase were used for sources of data. The PRISMA guidelines were followed. Clinical studies published after January 1990 were selected using strict eligibility criteria. Quality appraisal and data tabulation were performed using predetermined forms. Data were synthesised by narrative review and random-effects meta-analysis using standardised response means. Heterogeneity and bias were assessed., Results: Twelve studies (4,224 patients), including two randomised controlled trials, were reviewed. Despite an initial decline in QOL after CEA, quantitative and qualitative analysis of the SF-36 questionnaire showed all domains returned to baseline by 1 year. Preliminary data suggests that QOL after CAS does not have an initial decline, especially in physical health domains. QOL is similar between CEA and CAS at 1 year. Comparisons to reference populations are inconclusive. Meta-analysis was limited by significant statistical and methodological heterogeneity., Conclusions: Revascularisation by CEA or CAS maintains preoperative QOL. There are minimal differences between CEA and CAS. This review reaffirms the success of carotid revascularisation in preventing the devastating consequences of stroke on QOL and functional status. Guidelines for future studies are provided., (Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: Stress experienced during childhood or adulthood has been associated with cardiovascular disease (CVD), but it is not clear whether associations are already prevalent on a subclinical cardiovascular level. This study investigates associations between indicators of life stress and subclinical CVD, and whether these are mediated by depression and anxiety., Methods: Subjects were 650 participants of the Netherlands Study of Depression and Anxiety, aged 20-66 years, with or without (27.5%) depressive and anxiety disorders. Life stress included childhood trauma, negative life events and recently experienced daily hassles or job strain. Subclinical CVD was measured as 1) carotid atherosclerosis (intima-media thickness and the presence of plaques) using B-mode ultrasonography, and 2) central arterial stiffness (heart rate normalized augmentation index) using calibrated radial applanation tonometry., Results: Increased central arterial stiffness was shown in subjects who had experienced childhood trauma (per SD increase: β=.07; p=.01), or reported recently experienced daily hassles (per SD increase: β=.06; p=.02), negative life events (per SD increase: β=.05; p=.03), or job strain (high versus low: β=.09; p=.01). Associations between life stress and arterial stiffness appeared to be partly mediated by severity of depressive and anxiety symptoms. No significant associations were found for childhood life events, nor between indicators of life stress and carotid atherosclerosis., Conclusions: Childhood trauma and recent life stress were associated with increased central arterial stiffness. This suggests that life stress - partly via depression and anxiety - might enhance the development and progression of CVD., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Successful treatment options for cancer result in more young long-term survivors prone for long-term complications. Carotid artery vasculopathy is a potential long-term complication after radiotherapy of the neck, resulting in cerebrovascular events and probably deficits in cognitive and motor functioning. Better insight into the underlying pathofysiology of radiotherapy induced carotid artery vasculopathy is needed for prognostic purposes and to develop preventive strategies., Methods/design: The current study is a prospective cohort study on the long-term cerebral and vascular complications after radiotherapy of the neck, in 103 patients treated for head and neck cancer, included in our study database between 2002 and 2008. Baseline protocol (before radiotherapy) included screening for cerebrovascular risk factors and intima media thickness measurement of carotid arteries by ultrasonography. Follow-up assessment more than 5 years after radiotherapy included screening of cerebrovascular risk factors, cerebrovascular events, neurological examination with gait and balance tests, extensive neuropsychological examination, self-report questionnaires, ultrasonography of the carotid arteries with measurement of intima media thickness and elastography, magnetic resonance imaging of the brain and magnetic resonance angiography of the carotid arteries., Discussion: The current study adds to the understanding of the causes and consequences of long-term cerebral and vascular changes after radiotherapy of the neck. These data will be helpful to develop a protocol for diagnostic and preventive strategies for long-term neurological complications in future head and neck cancer patients with anticipated radiotherapy treatment.

Objective: Only a few studies have investigated the changes in carotid intima-media thickness (IMT) over time, and uncertainties remain on the underlying mechanisms linking depression and subclinical atherosclerosis. We carried out a prospective cohort study to evaluate whether depression is associated with changes in carotid IMT in subjects with cardiac risk factors but free from coronary heart disease (CHD), and to what extent the atherogenicity of depression can be explained by inflammatory markers and autonomic nervous system dysfunction., Methods: During baseline and follow-up visits: all participants were asked to provide blood samples and compile a structured questionnaire; trained physicians assessed depression symptoms using Beck Depression Inventory (BDI); altered cardiac autonomic tone was measured using time-domain components of heart rate variability in 24 h Holter recordings; measurements of carotid IMT were carried out using B-mode ultrasound image acquisition. Logistic and linear regression analyses were used to adjust for potential confounders and explore potential mediators., Results: A total of 381 subjects completed the 5-year follow-up. The mean carotid IMT significantly increased in all subjects but the amount of increase was significantly larger among subjects with depression symptoms: mean IMT increased by 0.16±0.14 mm; 0.31±0.28 mm and 0.61±0.54 mm among the subjects with no, mild and moderate/severe depression, respectively (all p<0.01). The association between moderate/severe depression and IMT increase remained highly significant even after controlling for all the variables considered, however when both IL-6 and CRP were included in multivariate models the regression coefficient decreased by 42.3%. Some of the inflammation markers and autonomic nervous system dysfunction were also independently correlated with carotid IMT increase., Conclusion: Depression symptoms are independently associated with an accelerated progression of carotid IMT in subjects with CHD risk factors, and inflammation may substantially modulate the association between depression and carotid IMT progression., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objectives: To evaluate health-related quality of life (HRQoL) in patients with symptomatic carotid disease (amaurosis fugax, transient ischaemic attack, stroke); to compare it with that of the general population; to explore whether HRQoL depends on the severity of the disease and to investigate the possible association between some demographic and clinical characteristics of patients and HRQoL., Methods: This cross-sectional study involved 175 patients with symptomatic carotid atherosclerotic disease who were referred for endarterectomy between January 2011 and December 2011. HRQoL was measured using Medical Outcome Survey Short Form 36 (SF-36)., Results: In comparison to both referent populations, patients with carotid disease had significantly lower mean SF-36 scores for role-physical (41.6 vs. 61.5 and 67.8), social functioning (65.4 vs. 73.8 and 80.0), role-emotional (48.2 vs. 68.6 and 80.5) and mental health (51.5 vs. 61.9 and 66.0). The SF-36 scores were significantly lower in female patients with carotid disease than in men (for role-physical 32.3 vs. 46.5; for bodily pain 57.0 vs. 73.0; for general health 55.6 vs. 61.5; for vitality 55.4 vs. 60.1; for social functioning 57.1 vs. 69.8 and for role-emotional 37.2 vs. 54.1). Significantly lower SF-36 scores were also found in patient with comorbidity (for physical functioning 68.1 vs. 77.7; for role-physical 35.1 vs. 52.3; for bodily pain 62.6 vs. 75.4; for general health 56.8 vs. 63.8; for social functioning 61.9 vs. 71.0, for role-emotional 41.6 vs. 59.1and for mental health 52.5 vs 49.8). In a multivariable analysis, education, occupation, body mass index, metabolic syndrome and severity of the disease had a weak influence on patients' HRQoL, while age, marital status, smoking, alcohol consumption, physical activity and the degree of carotid stenosis had no effect on patients' HRQoL. The SF-36 scores did not substantially change after adjustment for confounding variables., Conclusions: Patients with symptomatic carotid disease had poorer HRQoL, especially its mental components, than the general population. The severity of the disease was significantly associated only with the SF-36 role-physical subscale. HRQoL in patients with symptomatic carotid disease was poorer in women than in men, and was not affected by age and other demographic and clinical characteristics of patients.

Background: Carotid atherosclerosis has been suggested to be involved in cognitive decline., Methods: The Epidemiology of Hearing Loss Study is a longitudinal study of aging among Beaver Dam residents, WI. In 1998-2000, carotid intima-media thickness (IMT) and plaque were measured by ultrasound; cognitive function was measured by the Mini-Mental State Examination (MMSE). Follow-up examinations were conducted in 2003-2005 and 2009-2010. Incidence of cognitive impairment was defined as an MMSE score <24 or reported physician-diagnosed dementia during the follow-up. In the last examination, five additional cognitive tests were added. The associations of carotid atherosclerosis with incident cognitive impairment and cognitive test performance ten years later were evaluated., Results: A total of 1651 participants (mean age 66.8 years, 41% men) without cognitive impairment at baseline were included in the incidence analysis. IMT was associated with incidence of cognitive impairment after multiple adjustments (hazard ratio: 1.09, p = 0.02 for each 0.1 mm increase in IMT). A total of 1311 participants with atherosclerosis data at baseline had the additional cognitive tests 10 years later. Larger IMT was associated with longer time to complete the Trail-Making Test-part B after multiple adjustments (0.1 mm IMT: 2.3 s longer, p = 0.02). Plaque was not associated with incident cognitive impairment or cognitive test performance 10 years later., Conclusions: In this population-based longitudinal study, carotid IMT was associated with a higher risk of developing cognitive impairment during the 10-year follow-up, and was associated with poorer performance in a test of executive function 10 years later., (Published by Elsevier Ireland Ltd.)

Objective: Carotid arterial wall thickness, measured as intima-media thickness (IMT), is an early subclinical indicator of cardiovascular disease. Few studies have investigated the association of psychological factors with IMT across multiple ethnic groups and by sex., Methods: We included 6561 men and women (2541 whites, 1790 African Americans, 1436 Hispanics, and 794 Chinese) aged 45 to 84 years who took part in the first examination of the Multi-Ethnic Study of Atherosclerosis. Associations of trait anger, trait anxiety, and depressive symptoms with mean values of common carotid artery (CCA) and internal carotid artery (ICA) IMTs were investigated using multivariable regression and logistic models., Results: In age-, sex-, and race/ethnicity-adjusted analyses, the trait anger score was positively associated with CCA and ICA IMTs (mean differences per 1-standard deviation increment of trait anger score were 0.014 [95% confidence interval {CI} = 0.003-0.025, p = .01] and 0.054 [95% CI = 0.017-0.090, p = .004] for CCA and ICA IMTs, respectively). Anger was also associated with the presence of carotid plaque (age-, sex-, and race/ethnicity-adjusted odds ratio per 1-standard deviation increase in trait anger = 1.27 [95% CI = 1.06-1.52]). The associations of the anger score with thicker IMT were attenuated after adjustment for covariates but remained statistically significant. Associations were stronger in men than in women and in whites than in other race/ethnic groups, but heterogeneity was only marginally statistically significant by race/ethnicity. There was no association of depressive symptoms or trait anxiety with IMT., Conclusions: Only one of the three measures examined was associated with IMT, and the patterns seemed to be heterogeneous across race/ethnic groups.

Objective: We examine associations between the perception of ongoing psychological demands by ecological momentary assessment (EMA) and 6-year changes in carotid artery atherosclerosis by ultrasonography., Methods: A total of 270 initially healthy participants collected ambulatory blood pressure (ABP) and recorded their daily experiences, using electronic diaries, during two 3-day periods. Mean intima-media thickness (IMT) and plaque were assessed in the carotid arteries using B-mode ultrasound at baseline and again during a 6-year follow-up (mean follow-up duration = 73 months)., Results: Among those who had no exposure to antihypertensive medications during the course of follow-up (n = 192), daily psychological demands were associated with greater progression of IMT as well as plaque, after adjusting for demographic and risk factor covariates. Associations between demands and plaque change were partially accounted for by ABP differences among those reporting high demands. Among those who were employed at baseline (n = 117), 6-year IMT changes were more strongly associated with ratings of daily demands than with traditional measures of occupational stress., Conclusions: These data support the role of psychological demands as a correlate of subclinical atherosclerotic progression, they point to ABP as a potential mechanism facilitating these effects, and they highlight the utility of EMA measures for capturing daily psychological demands with potential effects on health.

The present work extends previous studies with the aim of developing the 4-vessel occlusion/internal carotid artery (4-VO/ICA) model of chronic cerebral hypoperfusion. The permanent occlusion of the vertebral arteries (VAs) and internal carotid arteries (ICAs) followed the sequence VA→ICA→ICA. The interstage interval (ISI, →), chronicity of 4-VO/ICA, and age of the animals may determine the success of the model with regard to neurohistological and behavioral outcomes. Using middle-aged rats, the present study evaluated (i) how brain damage evolves as the ISI is reduced and duration (i.e., "chronicity") of 4-VO/ICA is prolonged and (ii) how the duration of 4-VO/ICA affects retrograde memory performance. Male Wistar rats (12-15 months of age) were subjected to 4-VO/ICA with an ISI of 7, 5, 4, or 3 days, and hippocampal and cortical damage was examined 7, 30, and 90 days later. Using an ISI of 4 days, retrograde memory performance was assessed in the aversive radial maze after 4-VO/ICA with a duration of 7, 30, and 90 days. The severity of brain neurodegeneration and rate of mortality progressively increased as the ISI length decreased from 7 to 3 days, an effect that was not significantly altered by the chronicity of 4-VO/ICA. Permanent 4-VO/ICA effectively caused retrograde amnesia, an effect that worsened as the chronicity of 4-VO/ICA was prolonged. The findings confirm and expand the notion that permanent, 3-stage 4-VO/ICA effectively produces extensive neurodegeneration and persistent learning/memory impairment in middle-aged rats and that the ISI length, more than the chronicity of 4-VO/ICA, determines the final results., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Few therapeutic options are available nowadays to improve the prognosis of patients with Alzheimer's disease (AD). There are rather several evidences in literature that controlling vascular risk factors may be an effective intervention for modifying the course of this disease. The aim of our study was to investigate the role of CRF in 50 patients with MCI according to Petersens's criteria, and to evaluate their influence on cognitive and behavioral features of the disease and on the development of dementia. Statistical analysis of the data showed that the 60% of the patients with MCI and CRF developed dementia, while 40% maintained the same cognitive conditions at the end of the study. Only 32% of the subjects without cardiovascular comorbidities developed dementia. The results of the study suggest that CRF play a key role in cognitive decline of patients with MCI. Patients with MCI and CRF showed not only worse cognitive performances, but also behavioral disorders, depression and functional disability. Patients with CRF had higher conversion rate to AD than the other group, with a mean disease-free period 3 months shorter than the control group., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: To determine whether unihemispheral hemodynamic failure is independently associated with cognitive impairment among participants in the National Institute of Neurological Disorders and Stroke-sponsored, multicenter, randomized clinical trial, Randomized Evaluation of Carotid Occlusion and Neurocognition (RECON)., Methods: Forty-three patients were randomized into RECON after recent symptomatic carotid artery occlusion and asymmetrically increased oxygen extraction fraction (OEF) by PET (OEF ratio >1.13), indicating stage II hemodynamic failure on the side of occlusion. The PET-positive patients were compared with 28 RECON-enrolled patients who met all clinical and radiographic inclusion/exclusion criteria but had no OEF asymmetry. A multivariable regression compared patients with PET OEF >1.13 or ≤1.13, stratifying by TIA vs. stroke as the qualifying event. The dependent variable was a composite neurocognitive score derived from averaging age-normalized z scores on a test battery that included global and internal carotid artery (ICA) side-relevant hemisphere-specific tests., Results: There were no differences in demographic, clinical, or radiologic characteristics between the PET-positive and PET-negative patients except for PET OEF asymmetry. The unadjusted average neurocognitive z score was -1.45 for the PET-positive and -1.25 for the PET-negative patients, indicating cognitive impairment in both groups but no difference between them (p = 0.641). After adjustment for age, education, side of occlusion, depression, and previous stroke, there was a significant difference between PET-positive and PET-negative patients among those with TIA as a qualifying event (average z score = -1.41 vs. -0.76, p = 0.040). Older age and right ICA side were also significant in this model., Conclusion: Hemodynamic failure is independently associated with cognitive impairment in patients with carotid occlusion. This finding establishes the physiologic parameter upon which the extracranial-intracranial bypass will be tested.

Background: Atherosclerosis may be associated with cognitive function; however the studies are few, especially among midlife adults., Methods: Participants in the beaver dam offspring study who had cognitive test data and gradable carotid artery ultrasound scans were included (n=2794, mean age: 49 years). Atherosclerosis was measured by carotid intima-media thickness (IMT) and the presence of plaque. Cognitive function was measured by the trail making test (TMT), grooved pegboard test (GPT) and mini-mental state examination (MMSE). Generalized cognitive function was defined by a summary score calculated from the TMT and GPT. Linear regression was used to evaluate the associations between carotid atherosclerosis and cognitive function tests., Results: Larger IMT was associated with lower GPT, MMSE and the summary score adjusting for multiple factors, the coefficients were: 13.8s (p<0.0001), -0.6 (p=0.007), and 0.47 (p=0.01), respectively for 1mm increase in IMT. Plaque scores were significantly associated with TMT-B, GPT, MMSE, and the summary score adjusting for age, sex and education. The associations remained statistically significant after further adjustments except for the association with TMT-B, which was attenuated and no longer significant., Conclusions: Our results show the significant associations between markers of carotid atherosclerosis and cognitive function in a cohort of persons aged 21-84 years. Longitudinal studies are needed to further examine these associations., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: Depression and inflammation have been suggested to be involved in the atherosclerotic processes, but empirical evidence is mixed. We tested the hypothesis that depressive symptoms are associated with atherosclerosis only when combined with other risk factors, such as inflammation indicated by indoleamine 2,3-dioxygenase (IDO) activation., Methods: Participants were 544 women and 442 men (aged 24-39 years) who participated in the Young Finns Study medical examinations in 2001 and 2007. At baseline (in 2001), IDO activity (tryptophan and kynurenine ratio) and other biological and behavioral risk factors were assessed and depressive symptoms were determined using a modified 21-item Beck Depression Inventory. Carotid atherosclerosis was measured on the basis of carotid intimamedia thickness (IMT) at baseline and again in 2007., Results: In women, IDO activity moderated the association between depressive symptoms and IMT (p=0.02), so that a longitudinal association between depressive symptoms and IMT was found only in combination with high IDO activity (B=0.21, p=0.009). This association was robust to adjustment for other risk factors except body mass index and lipids which largely removed the association., Limitations: The results of this study need to be confirmed using larger data sets and studies using clinical cut-off point for depression., Conclusions: These data suggest that depressive symptoms are associated with preclinical y carotid atherosclerosis only if they are linked to inflammation, and that this association is present only in women. Underlying mechanisms are unknown but probably relate to adiposity., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Objective: To compare the effect on cognition of carotid artery stenting (CAS) and carotid endarterectomy (CEA) for symptomatic carotid artery stenosis., Methods: Patients randomized to CAS or CEA in the International Carotid Stenting Study (ICSS; ISRCTN25337470) at 2 participating centers underwent detailed neuropsychological examinations (NPE) before and 6 months after revascularization. Ischemic brain lesions were assessed with diffusion-weighted imaging before and within 3 days after revascularization. Cognitive test results were standardized into z scores, from which a cognitive sumscore was calculated. The primary outcome was the change in cognitive sumscore between baseline and follow-up., Results: Of the 1,713 patients included in ICSS, 177 were enrolled in the 2 centers during the substudy period, of whom 140 had an NPE at baseline and 120 at follow-up. One patient with an unreliable baseline NPE was excluded. CAS was associated with a larger decrease in cognition than CEA, but the between-group difference was not statistically significant: -0.17 (95% CI -0.38 to 0.03; p = 0.092). Eighty-nine patients had a pretreatment MRI and 64 within 3 days after revascularization. New ischemic lesions were found twice as often after CAS than after CEA (relative risk 2.1; 95% CI 1.0 to 4.4; p = 0.041)., Conclusions: Differences between CAS and CEA in effect on cognition were not statistically significant, despite a substantially higher rate of new ischemic lesions after CAS than after CEA., Classification of Evidence: This study provides Class III evidence that any difference between the effects of CAS and CEA on cognition at 6 months after revascularization is small.

Background: Depression increases the risk of subsequent vascular events in both cardiac and non-cardiac patients. Atherosclerosis, the underlying process leading to vascular events, has been associated with depression. This association, however, may be confounded by the somatic-affective symptoms being a consequence of cardiovascular disease. While taking into account the differentiation between somatic-affective and cognitive-affective symptoms of depression, we examined the association between depression and atherosclerosis in a community-based sample., Method: In 1261 participants of the Nijmegen Biomedical Study (NBS), aged 50-70 years and free of stroke and dementia, we measured the intima-media thickness (IMT) of the carotid artery as a measure of atherosclerosis and we assessed depressive symptoms using the Beck Depression Inventory (BDI). Principal components analysis (PCA) of the BDI items yielded two factors, representing a cognitive-affective and a somatic-affective symptom cluster. While correcting for confounders, we used separate multiple regression analyses to test the BDI sum score and both depression symptom clusters., Results: We found a significant correlation between the BDI sum score and the IMT. Cognitive-affective, but not somatic-affective, symptoms were also associated with the IMT. When we stratified for coronary artery disease (CAD), the somatic-affective symptom cluster correlated significantly with depression in both patients with and patients without CAD., Conclusions: The association between depressive symptoms and atherosclerosis is explained by the somatic-affective symptom cluster of depression. Subclinical vascular disease thus may inflate depressive symptom scores and may explain why treatment of depression in cardiac patients hardly affects vascular outcome.

Purpose: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a cerebral small vessel disease caused by mutations of the NOTCH3 gene. Marked variations in disease severity have raised the hypothesis that non-genetic factors may modulate the expressivity of the phenotype. The aim of the current study was to evaluate whether atherosclerosis, assessed by carotid duplex ultrasonography, is associated with variations in the clinical and MRI phenotype of CADASIL., Methods: Data from 144 consecutive patients enrolled in an ongoing prospective cohort study were collected. Degree of disability was assessed by the modified Rankin Scale, that of cognitive impairment by the Mattis Dementia Rating Scale (MDRS). The total volume of the brain, of lacunar lesions and of white matter hyperintensities, the number of cerebral microhemorrhages, and parameters derived from histograms of apparent diffusion coefficient were measured on cerebral MRI. Atherosclerosis was evaluated by B-mode ultrasonography of carotid arteries. Both the carotid intima-media thickness (cIMT) and the presence of carotid plaques or stenosis were recorded., Results: Higher cIMT was found to be independently associated with lower MDRS scores when this score was less than the quartile limit (p = 0.02). Only a trend for a positive association was detected between cIMT and the Rankin score (p = 0.06). There was no significant association between carotid markers and the occurrence of stroke or MRI parameters except for diffusion data. The mean and peak values of MRI diffusion histograms were found positively associated with the presence of plaques (p < 0.01)., Conclusion: The results suggest that the severity of atherosclerosis may relate to cognitive decline in CADASIL and that this effect is possibly related to the degree of microstructural cerebral tissue lesions. Longitudinal studies are needed to confirm these results., (Copyright © 2010 S. Karger AG, Basel.)

A large body of evidence links antagonism-related traits with cardiovascular outcomes, but less is known about how psychological traits are associated with intermediate markers of cardiovascular disease. Using a large, community-based sample from Sardinia, Italy (n=5614), this study examined how trait antagonism (low agreeableness) and its facets are associated with carotid artery intima-media thickness, a measure of arterial thickening. Controlling for demographic and cardiovascular risk factors, low agreeableness and, in particular, low straightforwardness and low compliance, were associated with greater carotid thickening, measured concurrently and prospectively, and with increases in intima-media thickness over 3 years. Indeed, those in the bottom 10% of agreeableness had a 40% increase in risk for elevated intima-media thickness. Although men have thicker arterial walls, women with antagonistic traits had similar carotid thickening as antagonistic men. Antagonistic individuals, especially those who are manipulative and aggressive, have greater increases in arterial thickening, independent of traditional cardiovascular risk factors.

This review encourages the reader to consider cerebral vascular disease beyond the traditional clinical end points of major motor and speech strokes and to consider the possible impact of embolic cerebral vascular disease on vascular cognitive decline. This article examines the issue of "silent" strokes in the relationship between the structural stability of atherosclerotic carotid plaque and the development of nonmotor symptomatology, including cognitive decline. It addresses the question of the role of carotid emboli in silent stroke and their cognitive sequelae. In a study of endarterectomy patients, we relate plaque elasticity and its development of mechanical strain features and thinning of stabilizing fibrous cap at the point of these mechanical strain features. The possibility that microemboli from such mechanically unstable carotid plaques could contribute to silent strokes led to a study of cognitive function in such patients. A linear relationship between the process of mechanically unstable areas of carotid plaques and cognitive decline suggests a contributory role for such a process in silent strokes.

Background: Intraoperative monitoring of cerebral ischemia with shunting during carotid endarterectomy (CEA) remains controversial. Our objective was to evaluate the sensitivity and specificity of BIS changes during carotid clamping in relation to shunted patients in awake CEA., Methods: Eighty CEAs under cervical block were included. There were two patient groups: with clinical signs of cerebral ischemia (shunted patients) and without signs of cerebral ischemia (nonshunted patients). Data were based on bispectral index (BIS) values and neurological monitoring at different surgery time points, with special attention paid during carotid clamping. BIS values were compared between shunted and nonshunted patients. Sensitivity and specificity, along with positive and negative predictive values of a percentage BIS value decrease during carotid clamping from baseline BIS values, were calculated in both patient groups., Results: Shunting was performed in 11 patients with cerebral ischemia at carotid clamping. Mean BIS values were 82.82+/-11.98 in shunted patients and 92.31+/-5.42 in nonshunted patients at carotid clamping (p<0.001). Relative decreased BIS values in relation to basal BIS values were 13.57% in shunted patients and 3.68% in nonshunted patients (p<0.05). The percentage decrease in BIS was 14%, sensitivity was 81.8% (95% CI 49.9-96.8), and specificity was 89.7% (95% CI 79.3-95.4)., Conclusion: BIS monitoring during carotid clamping is an easy, noninvasive method which correlates with cerebral ischemia in patients undergoing CEA. A decrease>or=14% from the basal BIS value presents a high negative predictive value, and ischemia is unlikely without a decrease. Nonetheless, a decrease may not always indicate cerebral ischemia with a low positive predictive value., (Copyright (c) 2010 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.)

Background: Acute mental stress may contribute to the cardiovascular disease progression via autonomic nervous system controlled negative effects on the endothelium. The joint effects of stress-induced sympathetic or parasympathetic activity and endothelial function on atherosclerosis development have not been investigated. The present study aims to examine the interactive effect of acute mental stress-induced cardiac reactivity/recovery and endothelial function on the prevalence of carotid atherosclerosis., Methods: Participants were 81 healthy young adults aged 24-39 years. Preclinical atherosclerosis was assessed by carotid intima-media thickness (IMT) and endothelial function was measured as flow-mediated dilatation (FMD) using ultrasound techniques. We also measured heart rate, respiratory sinus arrhythmia (RSA), and pre-ejection period (PEP) in response to the mental arithmetic and speech tasks., Results: We found a significant interaction of FMD and cardiac RSA recovery for IMT (p = 0.037), and a significant interaction of FMD and PEP recovery for IMT (p = 0.006). Among participants with low FMD, slower PEP recovery was related to higher IMT. Among individuals with high FMD, slow RSA recovery predicted higher IMT. No significant interactions of FMD and cardiac reactivity for IMT were found., Conclusions: Cardiac recovery plays a role in atherosclerosis development in persons with high and low FMD. The role of sympathetically mediated cardiac activity seems to be more important in those with impaired FMD, and parasympathetically mediated in those with relatively high FMD. The development of endothelial dysfunction may be one possible mechanism linking slow cardiac recovery and atherosclerosis via autonomic nervous system mediated effect.

Background and Purpose: Carotid atherosclerosis has been associated with increased risk of stroke and poorer cognitive performance in older adults. The relation of carotid atherosclerosis to cognitive impairment and MRI indices of ischemia and aging in midlife is less clear., Methods: We studied 1975 Framingham Offspring Study participants free of stroke and dementia with available carotid ultrasound, brain MRI, and neuropsychological testing. We related common and internal carotid artery intima-media thickness and internal carotid stenosis to large white matter hyperintensity (>1 SD above age-specific mean), total brain volume, hippocampal volume, silent cerebral infarcts, and neuropsychological measures of verbal memory, executive function, and nonverbal memory measures., Results: We observed that internal carotid artery intima-media thickness, but not common carotid artery intima-media thickness, was associated with higher prevalence of silent cerebral infarcts (OR, 1.21; 95% CI, 1.03-1.43; P<0.05), large white matter hyperintensity (OR, 1.19; 95% CI, 1.03-1.38; P<0.05), lower total brain volume (-0.05 per SD; P<0.05), and poorer performance in verbal memory (-0.06 per SD; P<0.05) and nonverbal memory measures (-0.08 per SD; P<0.01), but not with hippocampal volume. Internal carotid stenosis >or=25% was associated with a higher prevalence of large white matter hyperintensity (adjusted OR, 1.77; 95% CI, 1.25-2.53) and lower total brain volume (-0.11 per SD; P=0.042) but not with silent cerebral infarcts or hippocampal volume. Internal carotid stenosis >or=50% was associated with higher prevalence of silent cerebral infarcts (OR, 2.53; 95% CI, 1.17-5.44), large white matter hyperintensity (OR, 2.35; 95% CI, 1.08-5.13), and poorer performance on executive function (-0.39 per SD; P<0.05), but not with total brain volume or hippocampal volume., Conclusions: Carotid atherosclerosis markers were associated with MRI indices of brain ischemia and aging and with cognitive impairment in a community-based sample of middle-aged adults. Our data suggest that internal carotid artery intima-media thickness may be a better marker for cognitive impairment than common carotid artery intima-media thickness.

Aims: Recent studies have suggested an association between depression and subclinical atherosclerosis as measured by presence of carotid atherosclerotic plaque and increased intima-media thickening in non-clinical populations. Given the high prevalence of depression in patients with Type 1 diabetes and the diabetes-related risk factors for atherosclerosis, we hypothesized that this relation might also be of special relevance in Type 1 diabetic patients., Methods: Intima-media thickness (IMT) and the presence of plaques in the carotid arteries were quantitatively assessed by high-resolution ultrasound in 175 adults (89 men, 86 women) with an established diagnosis of Type 1 diabetes. Having been treated for depression or current Beck Depression Inventory scores > 10 were considered to indicate depression., Results: In men, the risk of plaque was higher in depressed subjects relative to non-depressed participants after adjustment for age, smoking status, systolic blood pressure, dyslipidaemia and body mass index [odds ratio (OR) 5.19; 95% confidence interval (CI) 1.29, 20.81]. Depressed women did not have an increased risk of plaque compared with non-depressed women (OR 0.97; 95% 95% CI 0.22, 4.34). We did not observe an association between depression and IMT, in men or in women., Conclusions: In line with previous research, our findings suggest a link between depression and subclinical atherosclerosis in Type 1 diabetic men, but not in women.

Background: Increased carotid artery intima-media thickness (IMT) is a non-invasive marker of systemic arterial disease. Increased IMT has been associated with atherosclerosis, abnormal arterial mechanics, myocardial infarction, and stroke. Given evidence of a relationship between cardiovascular health and attention-executive-psychomotor functioning, the purpose of this study was to examine IMT in relation to neuropsychological test performance in patients with a variety of cardiovascular diagnoses., Methods: One hundred and nine participants, ages 55 to 85, underwent neuropsychological assessment and B-mode ultrasound of the left common carotid artery. IMT was calculated using an automated algorithm based on a validated edge-detection technique. The relationship between IMT and measures of language, memory, visual-spatial abilities and attention-executive-psychomotor functioning was modeled using hierarchical linear regression analyses adjusted for age, education, sex, cardiovascular risk, current systolic blood pressure, and history of coronary artery disease (CAD)., Results: Increased IMT was associated with significantly lower performance in the attention-executive-psychomotor domain (IMT beta=-0.26, p<.01), independent of age, education, sex, cardiovascular risk, current systolic blood pressure, and CAD (F(10,100)=3.61, p<.001). IMT was not significantly related to language, memory, or visual-spatial abilities., Conclusions: Our findings suggest that, in patients with cardiovascular disease, IMT may be associated with the integrity of frontal subcortical networks responsible for attention-executive-psychomotor performance. Future studies are needed to clarify the mechanisms by which IMT affects cognition and examine potential interactions between increased IMT and other measures of cardiovascular health such as blood pressure variability, cardiac systolic performance, and systemic perfusion.

Objective: We examined the Type A behavior across developmental periods as a predictor of adult carotid artery intima-media thickness (IMT)., Methods and Results: In this prospective cohort study of 408 men and 606 women, socioeconomic background and biological risk factors of participants were assessed at baseline at age 6 to 18 years of age, Type A behavior (Hunter-Wolf A-B Rating Scale) at the 6-, 9-, and 21-year follow-ups (subjects being 12 to 24, 15 to 27, and 27 to 39 years, respectively), and carotid IMT, adulthood socioeconomic situation, and biological risk factors at the 21-year follow-up when participants were at age 27 to 39 years of age. In men, the eagerness-energy component of Type A behavior, measured at any time point, was associated with thicker carotid IMT (P<0.008, P<0.04, P<0.03, and P<0.02 for the first, second, and third assessment, and for the average score, respectively), and this association was independent of early and adult risk factors. In women, the hard-driving component at baseline (P<0.04) but not later was independently related to thinner carotid IMT. The other components of Type A behavior (impatience-aggression and leadership) were not associated with IMT., Conclusions: Eagerness-energy component of Type A behavior over different developmental transitions seems to be a robust predictor of IMT in men.