Associations of carotid atherosclerosis with cognitive function and brain health: Findings from a UK tri-ethnic cohort study (Southall and Brent Revisited).

Background: Cognitive function has an important role in determining the quality of life of older adults. Cardiovascular disease (CVD) is common in older people and may compromise cognitive performance; however, the extent to which this is related to carotid atherosclerosis is unclear. Aim: We investigated associations between carotid atherosclerosis and cognitive function and neuroimaging markers of brain health in a UK multi-ethnic community-based sample including older people of European, South Asian, and African-Caribbean ethnicity. Methods: Carotid plaques and intima-media thickness (cIMT) were assessed using ultrasound in 985 people (mean age 73.2y, 56 % male). Associations of carotid atherosclerosis with cognitive function (memory, executive function, language and CSI-D, a global measure of cognitive state) and neuroimaging measures (total brain volume, hippocampal volume, white matter (WM) lesion volume and coalescence score) were analysed using regression analyses, with and without adjustment for potential confounders using two models: 1) adjustment for age, sex, and ethnicity; 2) model 1 plus education, physical activity category, body mass index, hypertension, diabetes, total and high density lipoprotein cholesterol, atrial fibrillation, smoking, previous CVD, alcohol consumption, and presence of chronic kidney disease. Results: People with carotid plaque or higher cIMT had lower CSI-D score, poorer memory poorer executive function and higher WM lesion volume and coalescence. Language was poorer in people with plaque but was not correlated with cIMT. Associations with plaque were preserved after full adjustment (model 2) but relationships for cIMT were attenuated. Associations with other plaque characteristics were generally unconvincing after adjustment. Conclusions: This multi-ethnic cohort study provides evidence that presence of carotid plaque, is associated with poorer cognitive function and brain health.

Is 3D ultrasound reliable for the evaluation of carotid disease? A systematic review and meta-analysis.

AIM: Studies assessing the use of 3D ultrasound (3DUS) for the evaluation of carotid disease reported varying views among observers about its reliability vis-à-vis 2DUS or angiography; ratings provided ranged from poor to excellent. Thisstudy aims to systematically review and analyze the reliability of 3DUS for the evaluation of carotid disease. MATERIALS AND METHODS: The PubMed database was searched for studies that evaluated carotid disease (i.e. plaque measurements and characteristics and degree of stenosis) using 3DUS. RESULTS: Sixteen studies comprising a total of 918 stenosed carotids were reviewed and meta-analyzed. Data on intra- and inter-observer reproducibility and inter-method agreement (i.e. 3DUS vs 2D and 3DUS vs angiography) were analyzed. Overall analysis showed excellent intra- and inter-observer reproducibility (intraobserver: correlation coefficient r=0.88, 95% confidence intervals (CI) 0.84-0.92; intra-observer: r=0.91, 95% CI 0.87-0.95). The analysis also showed excellent agreement between 3DUS and 2DUS (r=0.89, 95% CI 0.83-0.95) and between 3DUS and angiography (r=0.73, 95% CI 0.44-0.1). CONCLUSION: 3DUS has excellent intra- and inter-observer reproducibility and excellent agreement with 2DUS and angiography for the evaluation of carotid disease. Further studies assessing the reliability ofcarotid plaque characteristics using 3DUS in symptomatic and asymptomatic patients are required.

Contrast-enhanced ultrasound for the evaluation of symptomatic and asymptomatic carotid plaques: A systematic review and meta-analysis.

BACKGROUND: Contrast-enhanced ultrasound (CEUS) is a promising imaging modality for the assessment of plaque vulnerability. We aimed to systematically review and meta-analyze the ability of CEUS parameters to differentiate between symptomatic and asymptomatic carotid plaques and to assess its reproducibility. METHODS: PubMed, EMBASE, and Cochrane Library databases were searched for studies that potentially evaluated carotid plaques using CEUS. From the initial 2870 searches, 11 relevant publications comprising a total of 821 carotid plaques were reviewed. Data on CEUS parameters including quantitative and semi-quantitative parameters were extracted and analyzed. RESULTS: The overall analysis showed significantly higher CEUS parameters in symptomatic carotid plaques compared to asymptomatic carotid plaques (standardised mean difference (SMD) .95, 95% confidence interval (CI) .56-1.27, p < .01). Intra and inter-observer reproducibility of quantitative CEUS parameters were excellent (intra-observer, r = .95, 95% CI .87-1; inter-observer, r = .93, 95% CI .80-.1). Semi-quantitative CEUS parameters showed good intra-observer reliability and moderate inter-observer reliability (intra-observer, r = .77, 95% CI .64-.89; inter-observer, r = .75, 95% CI .61-.89). Heterogeneity among studies compared CEUS parameters in symptomatic and asymptomatic plaques and studies assessed inter-observer reproducibility, and significant biases in studies assessing CEUS reproducibility were present. CONCLUSION: CEUS is a useful vascular imaging method to differentiate between symptomatic and asymptomatic carotid plaques with moderate to excellent reproducibility. Quantitative CEUS analysis appeared to be more sensitive and reliable in assessing carotid plaques than semi-quantitative parameters. Further longitudinal prospective trials evaluating carotid plaque in asymptomatic population using CEUS to determine plaque characteristics that can become symptomatic are required.

Is carotid artery atherosclerosis associated with poor cognitive function assessed using the Mini-Mental State Examination? A systematic review and meta-analysis.

OBJECTIVES: To determine associations between carotid atherosclerosis assessed by ultrasound and the Mini-Mental State Examination (MMSE), a measure of global cognitive function. DESIGN: Systematic review and meta-analysis. METHODS: MEDLINE and EMBASE databases were searched up to 1 May 2020 to identify studies assessed the associations between asymptomatic carotid atherosclerosis and the MMSE. Studies reporting OR for associations between carotid plaque or intima-media thickness (cIMT) and dichotomised MMSE were meta-analysed. Publication bias of included studies was assessed. RESULTS: A total of 31 of 378 reviewed articles met the inclusion criteria; together they included 27 738 participants (age 35-95 years). Fifteen studies reported some evidence of a positive association between measures of atherosclerosis and poorer cognitive performance in either cross-sectional or longitudinal studies. The remaining 16 studies found no evidence of an association. Seven cross-sectional studies provided data suitable for meta-analysis. Meta-analysis of three studies that assessed carotid plaque (n=3549) showed an association between the presence of plaque and impaired MMSE with pooled estimate for the OR (95% CI) being 2.72 (0.85 to 4.59). An association between cIMT and impaired MMSE was reported in six studies (n=4443) with a pooled estimate for the OR (95% CI) being 1.13 (1.04 to 1.22). Heterogeneity across studies was moderate to small (carotid plaque with MMSE, I2=40.9%; cIMT with MMSE, I2=4.9%). There was evidence of publication bias for carotid plaque studies (p=0.02), but not cIMT studies (p=0.2). CONCLUSIONS: There is some, limited cross-sectional evidence indicating an association between cIMT and poorer global cognitive function assessed with MMSE. Estimates of the association between plaques and poor cognition are too imprecise to draw firm conclusions and evidence from studies of longitudinal associations between carotid atherosclerosis and MMSE is limited. PROSPERO REGISTRATION NUMBER: CRD42021240077.

Carotid atherosclerosis in people of European, South Asian and African Caribbean ethnicity in the Southall and Brent revisited study (SABRE).

Background: Atherosclerotic cardiovascular disease (ASCVD) risk differs by ethnicity. In comparison with Europeans (EA) South Asian (SA) people in UK experience higher risk of coronary heart disease (CHD) and stroke, while African Caribbean people have a lower risk of CHD but a higher risk of stroke. Aim: To compare carotid atherosclerosis in EA, SA, and AC participants in the Southall and Brent Revisited (SABRE) study and establish if any differences were explained by ASCVD risk factors. Methods: Cardiovascular risk factors were measured, and carotid ultrasound was performed in 985 individuals (438 EA, 325 SA, 228 AC). Carotid artery plaques and intima-media thickness (cIMT) were measured. Associations of carotid atherosclerosis with ethnicity were investigated using generalised linear models (GLMs), with and without adjustment for non-modifiable (age, sex) and modifiable risk factors (education, diabetes, hypertension, total cholesterol, HDL-C, alcohol consumption, current smoking). Results: Prevalence of any plaque was similar in EA and SA, but lower in AC (16, 16, and 6%, respectively; p < 0.001). In those with plaque, total plaque area, numbers of plaques, plaque class, or greyscale median did not differ by ethnicity; adjustment for risk factors had minimal effects. cIMT was higher in AC than the other ethnic groups after adjustment for age and sex, adjustment for risk factors attenuated this difference. Conclusion: Prevalence of carotid artery atherosclerotic plaques varies by ethnicity, independent of risk factors. Lower plaque prevalence in in AC is consistent with their lower risk of CHD but not their higher risk of stroke. Higher cIMT in AC may be explained by risk factors. The similarity of plaque burden in SA and EA despite established differences in ASCVD risk casts some doubt on the utility of carotid ultrasound as a means of assessing risk across these ethnic groups.