Association Between Carotid Plaque and Alzheimer's Disease Cerebrospinal Fluid Biomarkers and Cognitive Function in Cognitively Intact Adults: The CABLE Study.

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 Aß42 (ß = -1.173, p = 0.022), Aß42/Aß40 (ß = -0.092, p < 0.001), P-tau/Aß42 (ß = 0.110, p = 0.045), and T-tau/Aß42 (ß = 0.451, p = 0.010). A significant correlation between carotid plaque and cognition decline was also found in men (ß = -0.129, p = 0.021), and mediation analyses revealed that the effect of carotid plaque on cognitive function could be mediated by Aß42/Aß40 (proportion of mediation = 55.8%), P-tau/Aß42 (proportion of mediation = 51.6%, p = 0.015) and T-tau/Aß42 (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.

Associations of psychological factors with atherosclerosis and cardiovascular health in middle-age: the population-based Swedish CArdioPulmonary bioImage study (SCAPIS).

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 ß-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.

Association between carotid intima-media thickness and cognitive decline differs by race.

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.

Independent Associations Between Trait-Anger, Depressive Symptoms and Preclinical Atherosclerotic Progression.

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.

Subclinical carotid artery atherosclerosis and cognitive function in older adults.

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 (ß (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 .

Sexual Assault and Carotid Plaque Among Midlife Women.

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.

Carotid Atherosclerosis and Cognitive Function in a General Population Aged 63-65 Years: Data from the Akershus Cardiac Examination (ACE) 1950 Study.

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.

Early Emotional Symptoms Predicting Carotid Atherosclerosis in Youth: Results From a Birth Cohort in Latin America.

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.

Association between carotid atheroma and cerebral cortex structure at age 73 years.

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.

Carotid circumferential wall stress is not associated with cognitive performance among individuals in late middle age: The Maastricht Study.

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 ±â€¯8 years, 55% men, 42.5% highly educated, blood pressure 137 ±â€¯19/77 ±â€¯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 (CWSpulsatile) and average (CWSmean) 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 CWSpulsatile nor CWSmean 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.

Cognitive function of patients with rheumatoid arthritis is associated with disease activity but not carotid atherosclerotic changes.

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 (ß=-0.415, p<0.001) or DAS28-ESR (ß=-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.

High-flow bypass with radial artery graft followed by internal carotid artery ligation for large or giant aneurysms of cavernous or cervical portion: clinical results and cognitive performance.

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.

Association of subclinical carotid atherosclerosis with immediate memory and other cognitive functions.

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.

Exposure to Violence and Carotid Artery Intima-Media Thickness in Mexican Women.

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.

Ultrasound Markers of Carotid Atherosclerosis and Cognition: The Northern Manhattan Study.

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 (ß=-0.60; P=0.04). APOE ε4 carriers with greater cIMT exhibited worse episodic memory (ß=-1.31; P=0.04), semantic memory (ß=-1.45; P=0.01), and processing speed (ß=-1.21; P=0.03). Participants with greater cIMT at baseline did not exhibit significantly greater cognitive decline after adjustment. APOE ε4noncarriers with greater cIMT exhibited greater declines in executive function (ß=-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.

Activation of GABAB2 subunits alleviates chronic cerebral hypoperfusion-induced anxiety-like behaviours: A role for BDNF signalling and Kir3 channels.

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.

Calcifications in the carotid siphon inversely associate with cognitive performance in stroke-free community dwellers living in rural Ecuador (The Atahualpa Project).

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.

Patients with carotid atherosclerosis who underwent or did not undergo carotid endarterectomy: outcome on mood, cognition and quality of life.

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.

Subclinical carotid artery atherosclerosis and performance on cognitive tests in middle-aged adults: Baseline results from the ELSA-Brasil.

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 (ß = -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.