Long-Term Survival, Causes of Death, and Trends in 5-Year Mortality After Intracerebral Hemorrhage: The Tromsø Study.

BACKGROUND AND PURPOSE: Data on long-term survival after intracerebral hemorrhage (ICH) are scarce. In a population-based nested case-control study, we compared long-term survival and causes of death within 5 years in 30-day survivors of first-ever ICH and controls, assessed the impact of cardiovascular risk factors on 5-year mortality, and analyzed time trend in 5-year mortality in ICH patients over 2 decades. METHODS: We included 219 participants from the population-based Tromsø Study, who after the baseline participation had a first-ever ICH between 1994 to 2013 and 1095 age- and sex-matched participants without ICH. Cumulative survival was presented using the Kaplan-Meier method. Hazard ratios (HRs) for mortality and for the association between cardiovascular risk factors and 5-year mortality in 30-day survivors were estimated by stratified Cox proportional hazards models. Trend in 5-year mortality was assessed by logistic regression. RESULTS: Risk of death during follow-up (median time, 4.8 years) was increased in the ICH group compared with controls (HR, 1.62 [95% CI, 1.27-2.06]). Cardiovascular disease was the leading cause of death, with a higher proportion in ICH patients (22.9% versus 9.0%; P<0.001). Smoking increased the risk of 5-year mortality in cases and controls (HR, 1.59 [95% CI, 1.15-2.19]), whereas serum cholesterol was associated with 5-year mortality in cases only (HR, 1.39 [95% CI, 1.04-1.86]). Use of anticoagulants at ICH onset increased the risk of death (HR, 2.09 [95% CI, 1.09-4.00]). There was no difference according to ICH location (HR, 1.15 [95% CI, 0.56-2.37]). Five-year mortality did not change during the study period (odds ratio per calendar year, 1.01 [95% CI, 0.93-1.09]). CONCLUSIONS: Survival rates were significantly lower in cases than in controls, driven by a 2-fold increased risk of cardiovascular death. Smoking, serum cholesterol, and use of anticoagulant drugs were associated with increased risk of death in ICH patients. Five-year mortality rates in ICH patients remained stable over time.

The association between anthropometric measures of adiposity and the progression of carotid atherosclerosis.

BACKGROUND: Few reports are available on the contribution of general and abdominal obesity to the progression of carotid atherosclerosis in late adulthood. This study investigated the impact of four simple anthropometric measures of general and abdominal obesity on the progression of carotid atherosclerosis and the extent to which the association between adiposity and the progression of plaque burden is mediated by cardiometabolic markers. METHODS: Four thousand three hundred forty-five adults (median age 60) from the population-based Tromsø Study were followed over 7 years from the first carotid ultrasound screening to the next. The progression of carotid atherosclerosis was measured in three ways: incidence of plaques in previously plaque-free participants; change in the number of plaques; and total plaque area (TPA). We used generalised linear models to investigate the association between each adiposity measure - body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) - and each outcome. Models were adjusted for potential confounders (age, sex, smoking, education, physical activity). The pathways through which any associations observed might operate were investigated by further adjusting for cardiometabolic mediators (systolic blood pressure, cholesterol, and HbA1c). RESULTS: There was little evidence that adiposity was related to the formation of new plaques during follow-up. However, abdominal adiposity was associated with TPA progression. WHtR showed the largest effect size (mean change in TPA per one standard deviation (SD) increase in WHtR of 0.665 mm2, 95% confidence interval 0.198, 1.133) while BMI showed the smallest. Effect sizes were substantially reduced after the adjustment for potential mediators. CONCLUSIONS: Abdominal obesity indirectly measured with WC seems more strongly associated with the progression of TPA than general obesity. These associations appear to be largely mediated by known cardiometabolic markers.

Fish consumption, fish oil supplements and risk of atherosclerosis in the Tromsø study.

BACKGROUND: Whether long-chain n-3 PUFAs of marine origin have an anti-atherogenic effect in the general population has hardly been studied. In this population-based study, we hypothesized that fatty fish and fish oil intake protect against development of novel atherosclerotic plaques and is associated with reduced plaque size. METHODS: We obtained questionnaire-based information on fish consumption and carotid ultrasonography from 3900 persons aged 45-74 years. The questionnaires were validated by measuring serum concentrations of PUFAs and triglycerides in a subgroup. At follow-up seven years later, 2983 (76%) went through a second ultrasound scanning. Logistic regression and general linear models were used to analyze the outcome (plaque presence and plaque area) as a function of fish consumption, including analyses stratified on fish oil supplements. RESULTS: At baseline, lean fish intake < 1 time/week vs. 1-1.9 times/week was associated with risk of plaque (OR 1.34, 95% CI 1.03-1.76). Fatty fish intake and use of fish oil supplements were not statistically significantly associated with atherosclerosis at baseline. In persons without plaque at baseline, total fish consumption ≥3 times/week vs. 1-1.9 times/week was associated with risk of novel plaque (OR 1.32, 95% CI 1.01-1.73) and larger plaque area (1.76 mm2 vs. 1.46 mm2, p = 0.02) at follow-up. Adjustments for use of fish oil supplements had no impact on the associations, and no interactions were seen between total, fatty or lean fish consumption and fish oil intake. CONCLUSIONS: We found no protective effect of fatty fish eating or fish oil supplements on atherosclerotic plaque formation or plaque area in a general population. Lean fish consumption was associated with a reduced risk for plaque in cross-sectional analysis, suggesting that the beneficial effects of fish consumption on atherosclerosis may be mediated through other mechanisms than n-3 PUFAs.

Declining Incidence of Ischemic Stroke: What Is the Impact of Changing Risk Factors? The Tromsø Study 1995 to 2012.

BACKGROUND AND PURPOSE: It is proposed that 20% to 40% of the decline in first-ever stroke incidence is attributed to the improvement of risk factor control. We estimated the impact of modifiable cardiovascular risk factors on the changing incidence of ischemic stroke (IS) between 1995 and 2012, using individual person data from repeated surveys in a general population. METHODS: The proportion of the IS incidence decline explained by change in each risk factor over time was estimated from 1995 to 2012 by Poisson regression among 26 329 participants who attended the fourth Tromsø survey in 1994 to 1995. Hazard ratios for IS were estimated with Cox proportional hazards regression among 27 936 participants who attended at least 1 of the Tromsø surveys in 1994 to 1995, 2001, or 2007 to 2008. Age- and sex-adjusted means or prevalences of risk factors over time were estimated by generalized estimating equations. RESULTS: There were 1226 first-ever IS during 367 636 person-years of follow-up. Changes in cardiovascular risk factors accounted for 57% of the decrease in IS incidence from 1995 to 2012. The most important contributors were decreasing mean systolic blood pressure and smoking prevalence, accounting for 26% and 17% of the observed decline, respectively. Conversely, increasing diabetes mellitus prevalence contributed negatively to the declining IS incidence. CONCLUSIONS: Changes in cardiovascular risk factors explained 57% of the decrease in IS incidence from 1995 to 2012. Reduction in systolic blood pressure and prevalence of smoking were the most important contributors.

Time trends in incidence and case fatality of ischemic stroke: the tromsø study 1977-2010.

BACKGROUND AND PURPOSE: Ischemic stroke incidence has declined in industrialized countries the last decades, with possible exception for the youngest age groups. We estimated age- and sex-specific trends in incidence and case fatality of first-ever ischemic stroke between 1977 and 2010 in a Norwegian municipality. METHODS: Age-adjusted time trends in incidence from 1977 to 2010 were estimated by fractional polynomial and Poisson regression, and case fatality by logistic regression in 36 575 participants of the population-based Tromsø Study. RESULTS: There were 1214 first-ever ischemic strokes within a total follow-up time of 611 176 person-years. The overall age- and sex-adjusted incidence decreased by 24% in 1995 to 2010. In women aged 30 to 49 years, the incidence increased significantly from 1980 to 2010. In men aged 30 to 49 years, there was a nonsignificant, rising trend from 1977 to 2010. Men aged 50 to 64 years had similar incidence in 2010 compared with 1989. From the mid-1990s to 2010, the incidence declined significantly in women aged 50 to 74 years and in men aged 65 to 74 years, but remained stable in those aged ≥75 years. Case fatality decreased significantly in men aged 30 to 84 years from 1995 to 2010, whereas there was no significant change in women. CONCLUSIONS: Age-adjusted incidence of first-ever ischemic stroke increased in young women, declined in women aged 50 to 74 years and men aged 65 to 74 years and remained stable among the oldest. Case fatality declined in men aged 30 to 84 years, but not in women.

Carotid atherosclerosis predicts future myocardial infarction but not venous thromboembolism: the Tromso study.

OBJECTIVE: Recent studies have suggested that arterial and venous thrombosis share common risk factors. Although carotid atherosclerosis is associated with arterial cardiovascular events, its role in venous thromboembolic disease is unclear. We wanted to investigate and compare the effect of carotid atherosclerosis on the risk of myocardial infarction (MI) and venous thromboembolism (VTE) in a general population, taking into account competing risks. APPROACH AND RESULTS: Mean intima-media thickness and total plaque area in the right carotid artery were measured with ultrasound in 6257 people aged 25 to 84 years who participated in a population-based health study, the Tromsø Study, from 1994 to 1995. Incident MI and VTE events were registered from date of enrollment to end of follow-up on December 31, 2010. Cox proportional hazards regression models using age as time scale were used to estimate cause-specific hazard ratios with 95% confidence intervals for MI and VTE by increasing levels of intima-media thickness and total plaque area. There were 894 incident MI cases and 256 VTE events during a median of 15.4 years of follow-up. The risk of MI increased significantly across quartiles of mean intima-media thickness (P for trend <0.001) and with increasing total plaque area (P for trend <0.001), but neither intima-media thickness (P for trend=0.94) nor total plaque area (P for trend=0.45) was associated with VTE risk in multivariable-adjusted analysis. CONCLUSIONS: In this study, carotid atherosclerosis was strongly associated with future MI but not with VTE. Our findings suggest that carotid atherosclerosis does not represent a link between arterial and venous thrombosis.

Long-term use of lipid-lowering drugs slows progression of carotid atherosclerosis: the Tromso study 1994 to 2008.

OBJECTIVE: Data on the effect of lipid-lowering drugs (LLD) on carotid atherosclerosis outside clinical trials are limited. The aim of this study was to determine the effect of LLD on change in carotid intima media thickness and total plaque area in a general population. APPROACH AND RESULTS: Subjects were 1532 women and 1442 men who participated in a longitudinal population-based study with ultrasound examination of intima media thickness and total plaque area in the right carotid artery at baseline and after 13 years follow-up. Long-term use of LLD was defined as use for >5 years, any-time use of LLD was defined as use at baseline or at 6 years or at 13 years of follow-up. In multivariable models adjusted for age, sex, systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, prevalent cardiovascular disease, and daily smoking, long-term use of LLD had a protective effect on progression of both intima media thickness (ß=-0.0387 mm; P=0.002) and total plaque area (ß=-0.400 mm(2); P=0.006). There was a weaker protective effect of any-time use of LLD on progression of intima media thickness (ß=-0.024 mm; P=0.046) and total plaque area (ß=-0.318 mm(2); P=0.06). CONCLUSIONS: LLD protected against progression of carotid atherosclerosis. The protective effect was strongest in long-term users.

Safety and efficacy of tenecteplase in patients with wake-up stroke assessed by non-contrast CT (TWIST): a multicentre, open-label, randomised controlled trial.

BACKGROUND: Current evidence supports the use of intravenous thrombolysis with alteplase in patients with wake-up stroke selected with MRI or perfusion imaging and is recommended in clinical guidelines. However, access to advanced imaging techniques is often scarce. We aimed to determine whether thrombolytic treatment with intravenous tenecteplase given within 4·5 h of awakening improves functional outcome in patients with ischaemic wake-up stroke selected using non-contrast CT. METHODS: TWIST was an investigator-initiated, multicentre, open-label, randomised controlled trial with blinded endpoint assessment, conducted at 77 hospitals in ten countries. We included patients aged 18 years or older with acute ischaemic stroke symptoms upon awakening, limb weakness, a National Institutes of Health Stroke Scale (NIHSS) score of 3 or higher or aphasia, a non-contrast CT examination of the head, and the ability to receive tenecteplase within 4·5 h of awakening. Patients were randomly assigned (1:1) to either a single intravenous bolus of tenecteplase 0·25 mg per kg of bodyweight (maximum 25 mg) or control (no thrombolysis) using a central, web-based, computer-generated randomisation schedule. Trained research personnel, who conducted telephone interviews at 90 days (follow-up), were masked to treatment allocation. Clinical assessments were performed on day 1 (at baseline) and day 7 of hospital admission (or at discharge, whichever occurred first). The primary outcome was functional outcome assessed by the modified Rankin Scale (mRS) at 90 days and analysed using ordinal logistic regression in the intention-to-treat population. This trial is registered with EudraCT (2014-000096-80), ClinicalTrials.gov (NCT03181360), and ISRCTN (10601890). FINDINGS: From June 12, 2017, to Sept 30, 2021, 578 of the required 600 patients were enrolled (288 randomly assigned to the tenecteplase group and 290 to the control group [intention-to-treat population]). The median age of participants was 73·7 years (IQR 65·9-81·1). 332 (57%) of 578 participants were male and 246 (43%) were female. Treatment with tenecteplase was not associated with better functional outcome, according to mRS score at 90 days (adjusted OR 1·18, 95% CI 0·88-1·58; p=0·27). Mortality at 90 days did not significantly differ between treatment groups (28 [10%] patients in the tenecteplase group and 23 [8%] in the control group; adjusted HR 1·29, 95% CI 0·74-2·26; p=0·37). Symptomatic intracranial haemorrhage occurred in six (2%) patients in the tenecteplase group versus three (1%) in the control group (adjusted OR 2·17, 95% CI 0·53-8·87; p=0·28), whereas any intracranial haemorrhage occurred in 33 (11%) versus 30 (10%) patients (adjusted OR 1·14, 0·67-1·94; p=0·64). INTERPRETATION: In patients with wake-up stroke selected with non-contrast CT, treatment with tenecteplase was not associated with better functional outcome at 90 days. The number of symptomatic haemorrhages and any intracranial haemorrhages in both treatment groups was similar to findings from previous trials of wake-up stroke patients selected using advanced imaging. Current evidence does not support treatment with tenecteplase in patients selected with non-contrast CT. FUNDING: Norwegian Clinical Research Therapy in the Specialist Health Services Programme, the Swiss Heart Foundation, the British Heart Foundation, and the Norwegian National Association for Public Health.

Risk factors for progression of carotid intima-media thickness and total plaque area: a 13-year follow-up study: the Tromsø Study.

BACKGROUND AND PURPOSE: Data on risk factors for progression of intima-media thickness (IMT) and plaque are scarce. The objective was to determine long-term risk factors for total plaque area (TPA) and IMT as well as risk factors for progression (ΔTPA and ΔIMT). METHODS: Subjects were 1307 men and 1436 women who participated in a longitudinal population-based study with ultrasound examination of the right carotid artery at baseline and after 13 years of follow-up. Total cholesterol, high-density lipoprotein cholesterol, blood pressure, body mass index, and information about smoking habits, prevalent diabetes, and cardiovascular disease were obtained at baseline. Carotid atherosclerosis was assessed as TPA and mean IMT of plaque-free segments of the common carotid artery. Associations between z-scores of risk factors and carotid atherosclerosis were assessed in multiple linear regression models. RESULTS: In multivariable models, total cholesterol, systolic blood pressure, and smoking were stronger predictors of follow-up TPA than of IMT, whereas sex and age were stronger predictors of IMT. Total cholesterol (standardized ß=0.081), systolic blood pressure (standardized ß=0.062), and smoking (standardized ß=0.107) were significant predictors of ΔTPA, whereas only total cholesterol (standardized ß=0.084) was an independent predictor of ΔIMT. The variance explained by traditional cardiovascular risk factors was somewhat greater for TPA than for IMT. CONCLUSIONS: The cardiovascular risk factors total cholesterol, smoking, and systolic blood pressure were stronger long-term predictors of TPA and TPA progression than for IMT and IMT progression.

The metabolic syndrome and progression of carotid atherosclerosis over 13 years. The Tromsø study.

BACKGROUND: The metabolic syndrome (MetS) is associated with increased risk of cardiovascular disease. In this study, we examine if metabolic syndrome predicts progression of atherosclerosis over 13 years. METHODS: Participants were 1442 men and 1532 women in the population-based Tromsø Study who underwent carotid ultrasound examinations at baseline in the 4th (1994-5) and at follow-up in the 6th survey (2007-8). Of these, 278 men and 273 women fulfilled the criteria for the MetS, defined according to a modified version of the National Cholesterol Education Program Adult Treatment Panel III (NCEP, ATPIII). Carotid atherosclerosis was assessed as total plaque area (TPA) and mean intima-media thickness (IMT) at follow-up and as change in IMT and TPA from baseline to follow-up. Associations between MetS and its components and carotid atherosclerosis were assessed in linear regression models adjusted for age, total cholesterol and daily smoking, stratified by sex. RESULTS: IMT and TPA levels at follow-up (p < 0.0001) and progression of TPA (p = 0.02) were higher in the MetS group compared to the non-MetS group. In stepwise multivariable models, MetS was associated with TPA (ß = 0.372 mm2, p = 0.009) and IMT (ß = 0.051 mm, p < 0.0001) in men, and with IMT (ß = 0.045 mm, p = 0.001) in women after 13 years of follow-up, but not with progression of IMT or TPA. In analyses stratified by age, MetS predicted progression of IMT (ß = 0.043 mm, p = 0.046) and TPA (ß = 1.02 mm2, p = 0.002) in men below 50 years of age. Hypertension was predictive of follow-up TPA and IMT in both genders and of progression of TPA in women. Impaired glucose tolerance was associated with follow up levels of IMT and TPA as well as progression in IMT in men. None of the other components of MetS were associated with progression of atherosclerosis. CONCLUSIONS: Subjects with MetS had higher levels of IMT and TPA at follow up than those without MetS. Mets predicted progression of IMT and TPA in those below 50 years of age, but not in other age groups, indicating that MetS may be involved in the initiation of the atherosclerotic process.

Carotid atherosclerosis predicts lower cognitive test results: a 7-year follow-up study of 4,371 stroke-free subjects - the Tromsø study.

BACKGROUND: Carotid artery atherosclerosis is a major risk factor for stroke and subsequent cognitive impairment. Prospective population studies have shown associations between carotid intima-media thickness (IMT) and stenosis and cognitive decline and dementia in elderly stroke-free persons, whereas results in the middle-aged are conflicting. METHODS: In this prospective population-based study, 4,371 stroke-free middle-aged participants underwent carotid ultrasound examination and assessment of vascular risk factors at baseline and were tested for cognitive function 7 years later. Associations between IMT, number of plaques and total plaque area and cognitive test scores on verbal memory test, digit symbol-coding test and tapping test were assessed in linear regression models. RESULTS: In the multivariable analyses adjusted for sex, age, education, depression and vascular risk factors, the presence of plaques was significantly associated with lower test scores on the verbal memory test (p = 0.01) and on the digit symbol-coding test (p = 0.03). The number of plaques (p = 0.01) and the total plaque area (p = 0.02) were associated with lower scores on the verbal memory test. No significant association was seen between common carotid artery IMT and cognitive test scores. The tapping test was not associated with the carotid ultrasound variables. CONCLUSIONS: In this middle-aged general population, subclinical carotid atherosclerosis measured as the presence of plaques, number of plaques and total plaque area were independent long-term predictors of lower cognitive test scores.

Carotid plaque area and intima-media thickness in prediction of first-ever ischemic stroke: a 10-year follow-up of 6584 men and women: the Tromsø Study.

BACKGROUND AND PURPOSE: Carotid plaque and intima-media thickness (IMT) are recognized as risk factors for ischemic stroke, but their predictive value has been debated and varies between studies. The purpose of this longitudinal population-based study was to assess the risk of ischemic stroke associated with plaque area and IMT in the carotid artery. METHODS: IMT and total plaque area in the right carotid artery were measured with ultrasound in 3240 men and 3344 women aged 25 to 84 years who participated in a population health study in 1994 to 1995. First-ever ischemic strokes were identified through linkage to hospital and national diagnosis registries, with follow-up until December 31, 2005. RESULTS: Incident ischemic strokes occurred in 7.3% (n=235) of men and 4.8% (n=162) of women. The hazard ratio for 1 SD increase in square-root-transformed plaque area was 1.23 (95% CI, 1.09-1.38; P=0.0009) in men and 1.19 (95% CI, 1.01-1.41; P=0.04) in women when adjusted for other cardiovascular risk factors. The multivariable-adjusted hazard ratio in the highest quartile of plaque area versus no plaque was 1.73 (95% CI, 1.19-2.52; P=0.004) in men and 1.62 (95% CI, 1.04-2.53; P=0.03) in women. The multivariable-adjusted hazard ratio for 1 SD increase in IMT was 1.08 (95% CI, 0.95-1.22; P=0.2) in men and 1.24 (95% CI, 1.05-1.48; P=0.01) in women. There were no differences in stroke risk across quartiles of IMT in multivariable analysis. CONCLUSIONS: In the present study, total plaque area appears to be a stronger predictor than IMT for first-ever ischemic stroke.

Atherosclerosis in abdominal aortic aneurysms: a causal event or a process running in parallel? The Tromsø study.

OBJECTIVE: The pathogenesis of abdominal aortic aneurysm (AAA) formation is poorly understood. We investigated the relationship between carotid, femoral, and coronary atherosclerosis and abdominal aortic diameter, and whether atherosclerosis was a risk marker for AAA. METHODS AND RESULTS: Ultrasound of the right carotid artery, the common femoral artery, and the abdominal aorta was performed in 6446 men and women from a general population. The burden of atherosclerosis was assessed as carotid total plaque area, common femoral lumen diameter, and self-reported coronary heart disease. An AAA was defined as maximal infrarenal aortic diameter > or =30 mm. No dose-response relationship was found between carotid atherosclerosis and abdominal aortic diameter <27 mm. However, significantly more atherosclerosis and coronary heart disease was found in aortic diameter > or =27 mm and in AAAs. The age- and sex-adjusted odds ratio (OR) (95% CI) for AAA in the top total plaque area quintile was 2.3 (1.5 to 3.4), as compared with subjects without plaques. The adjusted OR (95% CI) was 1.7 (1.1 to 2.6). No independent association was found between femoral lumen diameter and AAA. CONCLUSIONS: The lack of a consistent dose-response relationship between atherosclerosis and abdominal aortic diameter suggests that atherosclerosis may not be a causal event in AAA but develops in parallel with or secondary to aneurismal dilatation.

Are the currently used reference intervals for creatine kinase (CK) reflecting the general population? The Tromsø Study.

BACKGROUND: Laboratory reference intervals are not necessarily reflecting the range in the background population. This study compared creatine kinase (CK) reference intervals calculated from a large sample from a Norwegian population with those elaborated by the Nordic Reference Interval Project (NORIP). It also assessed the pattern of CK-normalization after standardized control analyses. METHODS: New upper reference limits (URL) CK values were calculated after exclusion of individuals with risk of hyperCKemia and including individuals with incidentally detected hyperCKemia after they had completed a standardized control analysis. After exclusion of 5924 individuals with possible causes of hyperCKemia, CK samples were analyzed in 6904 individuals participating in the 6th survey of The Tromsø Study. URL was defined as the 97.5 percentile. RESULTS: New URL in women was 207 U/L. In men <50 years it was 395 U/L and in men ≥50 years 340 U/L. In individuals with elevated CK, normalization grade after control analysis was inversely correlated to the CK level (p<0.04). CONCLUSIONS: URL CK values in women and in men <50 years of age were in accordance with URL CK values given by the NORIP. In men ≥50 years, a higher URL was found and the findings suggest an upward adjustment of URL in this age group.

Evaluation of Error Production in Animal Fluency and Its Relationship to Frontal Tracts in Normal Aging and Mild Alzheimer's Disease: A Combined LDA and Time-Course Analysis Investigation.

Semantic verbal fluency (VF), assessed by animal category, is a task widely used for early detection of dementia. A feature not regularly assessed is the occurrence of errors such as perseverations and intrusions. So far, no investigation has analyzed the how and when of error occurrence during semantic VF in aging populations, together with their possible neural correlates. The present study aims to address the issue using a combined methodology based on latent Dirichlet allocation (LDA) analysis for word classification together with a time-course analysis identifying exact time of errors' occurrence. LDA is a modeling technique that discloses hidden semantic structures based on a given corpus of documents. We evaluated a sample of 66 participants divided into a healthy young group (n = 24), healthy older adult group (n = 23), and group of patients with mild Alzheimer's disease (AD) (n = 19). We performed DTI analyses to evaluate the white matter integrity of three frontal tracts purportedly underlying error commission: anterior thalamic radiation, frontal aslant tract, and uncinate fasciculus. Contrasts of DTI metrics were performed on the older groups who were further classified into high-error rate and low-error rate subgroups. Results demonstrated a unique deployment of error commission in the patient group characterized by high incidence of intrusions in the first 15 s and higher rate of perseverations toward the end of the trial. Healthy groups predominantly showed very low incidence of perseverations. The DTI analyses revealed that the patients with AD committing high-error rate presented significantly more degenerated frontal tracts in the left hemisphere. Thus, our findings demonstrated that the appearance of intrusions, together with left hemisphere degeneration of frontal tracts, is a pathognomic trait of mild AD. Furthermore, our data suggest that the error commission of patients with AD arises from executive and working memory impairments related partly to deteriorated left frontal tracts.

Individual progression of carotid intima media thickness as a surrogate for vascular risk (PROG-IMT): Rationale and design of a meta-analysis project.

Carotid intima media thickness (IMT) progression is increasingly used as a surrogate for vascular risk. This use is supported by data from a few clinical trials investigating statins, but established criteria of surrogacy are only partially fulfilled. To provide a valid basis for the use of IMT progression as a study end point, we are performing a 3-step meta-analysis project based on individual participant data. Objectives of the 3 successive stages are to investigate (1) whether IMT progression prospectively predicts myocardial infarction, stroke, or death in population-based samples; (2) whether it does so in prevalent disease cohorts; and (3) whether interventions affecting IMT progression predict a therapeutic effect on clinical end points. Recruitment strategies, inclusion criteria, and estimates of the expected numbers of eligible studies are presented along with a detailed analysis plan.

Amyloid Plaques and Symptoms of Depression Links to Medical Help-Seeking due to Subjective Cognitive Decline.

BACKGROUND: Subjective cognitive decline (SCD) is associated with an increased risk of Alzheimer's disease (AD). However, patients reporting SCD to their general practitioner are not always referred to a memory clinic. OBJECTIVE: To investigate whether prior history of medical help-seeking is associated with AD biomarker abnormality, worse cognitive performance, and/or depressive symptoms in SCD. METHODS: We compared levels of cerebrospinal fluid (CSF) Aß1 - 42, cognitive performance, and depressive symptoms (15-item Geriatric Depression Scale, GDS-15) between healthy controls (n = 88), SCD with a history of medical help seeking (SCD-HS, n = 67), and SCD non help-seekers (SCD-NHS, n = 44). Cases with evidence of amyloid plaques (CSF Aß1 - 42 ≤708 ng/l) and symptoms of depression (GDS-15≥6) were determined in both SCD groups. RESULTS: The SCD-HS group had lower CSF Aß1 - 42 (p < 0.01), lower word list learning and memory recall (p < 0.0001), and an increased level of depressive symptoms (p < 0.0001) compared to controls and SCD-NHS cases. The SCD-HS group had more cases with symptoms of depression (n = 12, 18%) and amyloid plaques (n = 18, 27%) compared to SCD-NHS (n = 1, 2% and n = 7, 16%, respectively). None of the SCD-HS cases and only one SCD-NHS case had concurrent symptoms of depression and amyloid plaques. The SCD-HS cases showed equal word list learning and memory performance regardless of amyloid status or symptoms of depression. CONCLUSION: Medical help-seeking in SCD is associated with an increased risk of AD pathology or symptoms of depression. However, subtle memory deficits are seen in SCD help-seekers, also without amyloid plaques or symptoms of depression.

Progression of conventional cardiovascular risk factors and vascular disease risk in individuals: insights from the PROG-IMT consortium.

AIMS: Averaged measurements, but not the progression based on multiple assessments of carotid intima-media thickness, (cIMT) are predictive of cardiovascular disease (CVD) events in individuals. Whether this is true for conventional risk factors is unclear. METHODS AND RESULTS: An individual participant meta-analysis was used to associate the annualised progression of systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with future cardiovascular disease risk in 13 prospective cohort studies of the PROG-IMT collaboration (n = 34,072). Follow-up data included information on a combined cardiovascular disease endpoint of myocardial infarction, stroke, or vascular death. In secondary analyses, annualised progression was replaced with average. Log hazard ratios per standard deviation difference were pooled across studies by a random effects meta-analysis. In primary analysis, the annualised progression of total cholesterol was marginally related to a higher cardiovascular disease risk (hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.00 to 1.07). The annualised progression of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol was not associated with future cardiovascular disease risk. In secondary analysis, average systolic blood pressure (HR 1.20 95% CI 1.11 to 1.29) and low-density lipoprotein cholesterol (HR 1.09, 95% CI 1.02 to 1.16) were related to a greater, while high-density lipoprotein cholesterol (HR 0.92, 95% CI 0.88 to 0.97) was related to a lower risk of future cardiovascular disease events. CONCLUSION: Averaged measurements of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol displayed significant linear relationships with the risk of future cardiovascular disease events. However, there was no clear association between the annualised progression of these conventional risk factors in individuals with the risk of future clinical endpoints.

Relation of common carotid artery lumen diameter to general arterial dilating diathesis and abdominal aortic aneurysms: the Tromsø Study.

In a cross-sectional, population-based study in Tromsø, Norway, the authors investigated correlations between lumen diameter in the right common carotid artery (CCA) and the diameters of the femoral artery and abdominal aorta and whether CCA lumen diameter was a risk factor for abdominal aortic aneurysm (AAA). Ultrasonography was performed in 6,400 men and women aged 25-84 years during 1994-1995. An AAA was considered present if the aortic diameter at the level of renal arteries was greater than or equal to 35 mm, the infrarenal aortic diameter was greater than or equal to 5 mm larger than the diameter of the level of renal arteries, or a localized dilation of the aorta was present. CCA lumen diameter was positively correlated with abdominal aortic diameter (r = 0.3, P < 0.01) and femoral artery diameter (r = 0.2, P < 0.01). In a multivariable adjusted model, CCA lumen diameter was a significant predictor of AAA in both men and women (for the fifth quintile vs. the third, odds ratios were 1.9 (95% confidence interval: 1.2, 2.9) and 4.1 (95% confidence interval: 1.5, 10.8), respectively). Thus, CCA lumen diameter was positively correlated with femoral and abdominal aortic artery diameter and was an independent risk factor for AAA.

Carotid plaque compared with intima-media thickness as a predictor of coronary and cerebrovascular disease.

Atherosclerosis is the underlying cause of most myocardial infarction (MI) and ischemic strokes. B-mode ultrasound of carotid arteries provides measures of intima-media thickness (IMT) and plaques, both widely used as surrogate measures of cardiovascular disease. Although IMT and plaques are highly intercorrelated, IMT's role as a marker of atherosclerosis has been questioned, especially when measurements include the common carotid artery (CCA) only. Plaque and intima-media thickening may reflect different biological aspects of atherogenesis with distinctive relations to clinical vascular disease. Plaque measured in the carotid bulb or internal carotid artery is stronger related to hyperlipidemia and smoking and is a stronger predictor for MI, whereas CCA-IMT is stronger related to hypertension and ischemic stroke. Echolucent plaque morphology (ie, lipid-rich plaques) seems to increase the risk for MI and stroke. New evidence suggests that total plaque area is the most strongly predictive of cardiovascular risk of the ultrasound phenotypes.