A Tablet-PC-Based Cancellation Test Assessing Executive Functions in Older Adults.

OBJECTIVE: To examine older adults' performance on a newly developed tablet-PC-based cancellation test (e-CT) and to study its psychometric properties. METHODS: 94 older adults with normal cognitive functioning were recruited. The effects of age, education, sex, and experience with computer-based devices on the e-CT were examined. Construct validity was tested by correlating the e-CT with established measures of executive functions (EF) and episodic memory. Correlation coefficients were used to assess short-term test-retest reliablity. RESULTS: The mean age of participants was 74.6 (SD: 7.3) years and 78% were women. Sixty-nine percent had higher education level (> high school) and 76% used computer-based devices daily. The correct cancellations (CC) on the e-CT ranged from 18 to 56, with a mean (SD) of 40.3 (5.7). The CC was inversely correlated with advancing age (rs = -0.59, N = 94, p <0.001) and positively associated with higher education level (U(94) = 646.5, p = 0.02). No relationship was observed between the e-CT and sex or computer-based device experience. In multivariate analysis, only age remained significantly associated with CC (ß = -0.46, SE = 0.07, t = -6.47, df = 93, p <0.001). The e-CT correlated significantly with most of measures of EF. Highest correlations were found between the e-CT and the K-T test, a paper-and-pencil cancellation test (rs = 0.63, N = 90, p <0.001) and TMT-B (rs = -0.41, N = 85, p <0.001). The e-CT did not correlate with the RL-RI 16 episodic memory test. The correlation between the first and second e-CT indicated good reliability (rs = 0.89, N = 13, p <0.001). CONCLUSIONS: Results suggested that e-CT has good psychometric properties and may be useful for assessing EF in older adults.

Carotid plaque as a predictor of dementia in older adults: the Three-City Study.

BACKGROUND: The contribution of carotid atherosclerosis to incident dementia remains unclear. We examined the association between carotid plaques (CP) and common carotid intima media thickness (CCA-IMT) with incident dementia and its subtypes, and their added value for dementia risk prediction. METHODS: At baseline, 6025 dementia-free subjects aged 65-86 years underwent bilateral carotid ultrasonography measures of CP and plaque-free CCA-IMT. Subjects were followed-up over 7 years for the detection of dementia. RESULTS: After a mean 5.4 years of follow-up, 421 subjects developed dementia including 272 Alzheimer's disease and 83 vascular/mixed dementia (VaD). Only CP were independently related to VaD (HR(≥2 sites with plaques) = 1.92; 95% confidence interval or CI = 1.13-3.22) and improved VaD risk prediction (continuous Net Reclassification Index = 30.1%; 95% CI = 8.4-51.7) beyond known dementia risk factors. Accounting for stroke or competing risk by death marginally modified the results. CONCLUSION: In older adults, CP are independent predictors of incident VaD and may improve VaD risk prediction.

Carotid intima-media thickness progression to predict cardiovascular events in the general population (the PROG-IMT collaborative project): a meta-analysis of individual participant data.

BACKGROUND: Carotid intima-media thickness (cIMT) is related to the risk of cardiovascular events in the general population. An association between changes in cIMT and cardiovascular risk is frequently assumed but has rarely been reported. Our aim was to test this association. METHODS: We identified general population studies that assessed cIMT at least twice and followed up participants for myocardial infarction, stroke, or death. The study teams collaborated in an individual participant data meta-analysis. Excluding individuals with previous myocardial infarction or stroke, we assessed the association between cIMT progression and the risk of cardiovascular events (myocardial infarction, stroke, vascular death, or a combination of these) for each study with Cox regression. The log hazard ratios (HRs) per SD difference were pooled by random effects meta-analysis. FINDINGS: Of 21 eligible studies, 16 with 36,984 participants were included. During a mean follow-up of 7·0 years, 1519 myocardial infarctions, 1339 strokes, and 2028 combined endpoints (myocardial infarction, stroke, vascular death) occurred. Yearly cIMT progression was derived from two ultrasound visits 2-7 years (median 4 years) apart. For mean common carotid artery intima-media thickness progression, the overall HR of the combined endpoint was 0·97 (95% CI 0·94-1·00) when adjusted for age, sex, and mean common carotid artery intima-media thickness, and 0·98 (0·95-1·01) when also adjusted for vascular risk factors. Although we detected no associations with cIMT progression in sensitivity analyses, the mean cIMT of the two ultrasound scans was positively and robustly associated with cardiovascular risk (HR for the combined endpoint 1·16, 95% CI 1·10-1·22, adjusted for age, sex, mean common carotid artery intima-media thickness progression, and vascular risk factors). In three studies including 3439 participants who had four ultrasound scans, cIMT progression did not correlate between occassions (reproducibility correlations between r=-0·06 and r=-0·02). INTERPRETATION: The association between cIMT progression assessed from two ultrasound scans and cardiovascular risk in the general population remains unproven. No conclusion can be derived for the use of cIMT progression as a surrogate in clinical trials. FUNDING: Deutsche Forschungsgemeinschaft.

Association of Intima-Media Thickness Measured at the Common Carotid Artery With Incident Carotid Plaque: Individual Participant Data Meta-Analysis of 20 Prospective Studies.

Background The association between common carotid artery intima-media thickness (CCA-IMT) and incident carotid plaque has not been characterized fully. We therefore aimed to precisely quantify the relationship between CCA-IMT and carotid plaque development. Methods and Results We undertook an individual participant data meta-analysis of 20 prospective studies from the Proof-ATHERO (Prospective Studies of Atherosclerosis) consortium that recorded baseline CCA-IMT and incident carotid plaque involving 21 494 individuals without a history of cardiovascular disease and without preexisting carotid plaque at baseline. Mean baseline age was 56 years (SD, 9 years), 55% were women, and mean baseline CCA-IMT was 0.71 mm (SD, 0.17 mm). Over a median follow-up of 5.9 years (5th-95th percentile, 1.9-19.0 years), 8278 individuals developed first-ever carotid plaque. We combined study-specific odds ratios (ORs) for incident carotid plaque using random-effects meta-analysis. Baseline CCA-IMT was approximately log-linearly associated with the odds of developing carotid plaque. The age-, sex-, and trial arm-adjusted OR for carotid plaque per SD higher baseline CCA-IMT was 1.40 (95% CI, 1.31-1.50; I2=63.9%). The corresponding OR that was further adjusted for ethnicity, smoking, diabetes, body mass index, systolic blood pressure, low- and high-density lipoprotein cholesterol, and lipid-lowering and antihypertensive medication was 1.34 (95% CI, 1.24-1.45; I2=59.4%; 14 studies; 16 297 participants; 6381 incident plaques). We observed no significant effect modification across clinically relevant subgroups. Sensitivity analysis restricted to studies defining plaque as focal thickening yielded a comparable OR (1.38 [95% CI, 1.29-1.47]; I2=57.1%; 14 studies; 17 352 participants; 6991 incident plaques). Conclusions Our large-scale individual participant data meta-analysis demonstrated that CCA-IMT is associated with the long-term risk of developing first-ever carotid plaque, independent of traditional cardiovascular risk factors.

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.

Correction: Predictive value for cardiovascular events of common carotid intima media thickness and its rate of change in individuals at high cardiovascular risk - Results from the PROG-IMT collaboration.

[This corrects the article DOI: 10.1371/journal.pone.0191172.].

Predictive value for cardiovascular events of common carotid intima media thickness and its rate of change in individuals at high cardiovascular risk - Results from the PROG-IMT collaboration.

AIMS: Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk. METHODS AND RESULTS: From 31 cohorts with two CIMT scans (total n = 89070) on average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A) individuals with at least 3 cardiovascular risk factors without previous CVD events, (B) individuals with carotid plaques without previous CVD events, and (C) individuals with previous CVD events. Cox regression models were fit to estimate the hazard ratio (HR) of the combined endpoint (myocardial infarction, stroke or vascular death) per standard deviation (SD) of CIMT change, adjusted for CVD risk factors. These HRs were pooled across studies. In groups A, B and C we observed 3483, 2845 and 1165 endpoint events, respectively. Average common CIMT was 0.79mm (SD 0.16mm), and annual common CIMT change was 0.01mm (SD 0.07mm), both in group A. The pooled HR per SD of annual common CIMT change (0.02 to 0.43mm) was 0.99 (95% confidence interval: 0.95-1.02) in group A, 0.98 (0.93-1.04) in group B, and 0.95 (0.89-1.04) in group C. The HR per SD of common CIMT (average of the first and the second CIMT scan, 0.09 to 0.75mm) was 1.15 (1.07-1.23) in group A, 1.13 (1.05-1.22) in group B, and 1.12 (1.05-1.20) in group C. CONCLUSIONS: We confirm that common CIMT is associated with future CVD events in individuals at high risk. CIMT change does not relate to future event risk in high-risk individuals.

Can a tablet-based cancellation test identify cognitive impairment in older adults?

BACKGROUND AND OBJECTIVE: There has been a growing interest in using computerized cognitive assessment to detect age-related cognitive disorders. We have developed a tablet-based cancellation test (e-CT), previously shown as a reliable measure of executive functions and free of effect of familiarity with computer-based devices in healthy older adults. This study aimed to investigate the influence of demographics and current daily use of computer-based devices in older adults with Mild Cognitive Impairment (MCI) and Alzheimer's disease (AD). We further studied the ability of the e-CT to discriminate MCI and AD patients from older adults with normal cognition (NC). METHODS: The e-CT was administered to 325 older adults (NC = 112, MCI = 129, AD = 84). Subjects also performed the K-T test, a paper-and-pencil cancellation test from which the e-CT was developed. Multiple linear regression analyses were conducted to assess the contribution of demographics and current daily use of computer-based devices on the e-CT in patient groups. The Receiver Operating Characteristic (ROC) curves and the Area Under the Curve (AUC) were established to compare the efficacy of the e-CT and the K-T test to classify subjects into diagnostic groups. RESULTS: In the MCI group, age (B = -0.37, p<0.001) and current daily use of computer-based devices (B = 5.85, p<0.001) were associated with the number of correct cancellations of the e-CT. In the AD group, only current daily use of a computer-based device was a significant contributor (B = 6.28, p<0.001). The e-CT (AUC = 0.811; 95% confidence interval [CI]: 0.756-0.867) and the K-T (AUC = 0.837; CI: 0.787-0.887) showed good and comparable diagnostic accuracy to discriminate between MCI and NC subjects. To discriminate between NC and AD, both tests showed high diagnostic accuracy, with the AUC values of 0.923 (CI: 0.876-0.971) and 0.929 (95%CI: 0.886-0.972) for the e-CT and the K-T, respectively. CONCLUSION: The e-CT presents satisfying discriminative validity and is a promising tool for detection of early cognitive impairment in older adults.

Brain natriuretic peptide usefulness in very elderly dyspnoeic patients: the BED study.

AIMS: To evaluate the interest of brain natriuretic peptide (BNP) for heart failure (HF) diagnosis in very old patients. METHODS AND RESULTS: A total of 383 patients aged 80 years or older, hospitalized in geriatrics care for dyspnoea, had a BNP measurement at the acute phase. Independent cardiologists blinded to BNP values classified the patients into cardiac vs. respiratory aetiology according to the European Society of Cardiology guidelines. Mean (SD) age was 88.5 (5.4) years, 66% (n = 254) of patients were women, 62% (n = 238) had cardiac dyspnoea and 38% (n = 145) had respiratory dyspnoea. The BNP levels were significantly higher in the cardiac group (median = 385.5 ng/L, interquartile range = 174.0-842.0) than in the respiratory group (median = 172.0 ng/L, interquartile range = 70.8-428.0; P < 0.001). On its own, BNP showed poor discriminative ability [area under the curve (AUC) = 0.68; 95% confidence interval (CI) 0.62-0.73] for the diagnostic. In multivariate analysis, BNP remained independently associated with the cardiac aetiology after full-adjustment (odds ratio 1 log increase = 1.87; 95% CI 1.28-2.74), but did not improve the discrimination between the cardiac and the respiratory aetiologies (ΔAUC = 0.013, P = 0.16). In addition, although adding BNP to the other predictive covariates yielded a significant continuous NRI of 57.8% (95% CI 31.2-83.5%), the mean changes in individual predicted probabilities were too low (<3%) to be clinically relevant. CONCLUSION: In this population of very old patients with acute dyspnoea, despite being independently associated with the cardiac aetiology, BNP was not useful for better discriminating cardiac vs. respiratory origin.

Arterial stiffness and medial temporal lobe atrophy in elders with memory disorders.

OBJECTIVES: Hypertension is a risk factor for cognitive impairment and dementia. Arterial stiffness could be involved in the mechanisms of vascular cognitive impairment and in Alzheimer's disease. We examined the association between arterial stiffness, assessed by carotid-femoral pulse wave velocity (PWV), and medial temporal lobe (MTL) atrophy, a biomarker of Alzheimer's disease. METHODS: Elderly community-dwelling study participants (n = 149) with memory complaints were diagnosed with Alzheimer's disease (n = 62) or mild cognitive impairment (n = 87) at a memory clinic. PWV, peripheral and central blood pressure (SBP), and pulse pressure (PP) were measured. MTL was graded on MRI according to the Scheltens' scale. RESULTS: Mean age was 79.5 (SD = 5) years old, 36% of study participants were men. MTL was absent or discrete in 23.5%, moderate in 53.0% and severe in 23.5% of study participants. PWV was 9.3 (2.2) m/s in none or discrete, 11.1 (2.8) in moderate and 13.5 (4.0) in severe MTL atrophy (P < 0.0001). PWV, central SBP, and central PP were overall associated with MTL atrophy after adjustment for age, sex, antihypertensive treatments and white matter lesions, and further adjusted for mean BP for PWV, whereas peripheral SBP and PP were not associated with MTL atrophy. PWV was significantly associated with severe MTL atrophy [odds ratio = 3.69 (95% confidence interval = 1.69-8.05), P = 0.001] and marginally associated with moderate MTL atrophy [1.80 (0.92-3.53), P = 0.09]. Furthermore PWV was significantly associated with severe MTL atrophy in Alzheimer's disease and mild cognitive impairment study participants separately. CONCLUSION: The result of this study suggests a role of arterial stiffness in the pathogenesis of Alzheimer's disease.

Clinical utility of the K-T cancellation test in a memory clinic population.

BACKGROUND/AIM: The K-T cancellation test (K-T) has been validated as a measure of executive functions (EF) but its clinical utility has not yet been examined. This study aimed to validate K-T in a memory clinic setting by examining its capacity to discriminate older adults with normal cognition (NC) from those with mild cognitive impairment (MCI) and Alzheimer's disease (AD). METHOD: K-T was administered to 120 NC subjects, 146 patients with MCI, and 93 patients with AD. A one-way analysis of covariance was used to compare the correct cancellations of K-T between the groups. Linear regressions were run to identify significant demographic predictors of K-T for NC subjects and to determine the equation to calculate z scores for all subjects. The area under the curve (AUC), sensitivity (Se), specificity (Sp), and positive (PPV) and negative (NPV) predictive values were assessed to compare the diagnostic performance between K-T and the Mini-Mental State Examination (MMSE) for discrimination between NC subjects and patients with cognitive impairment. RESULTS: After adjusting for age, education, and gender, the groups were significantly different from each other regarding the number of correct cancellations of K-T, F(2, 353) = 116.6, p < .001, η(2)p = .40. Compared to the NC group (Z = 0, SD = 1), the mean z score was -1.52 for the MCI group and -2.53 for the AD group, suggesting impaired performance for the patient groups. K-T showed a better diagnostic performance for discrimination between the NC subjects and the patients with MCI (AUC = .83; 95% CI [.79, .88]; Se = .79; Sp = .74; PPV = .79; NPV = .74), compared to that of MMSE (AUC = .74, 95% CI [.68, .80]; Se = .68; Sp = .73; PPV = .79; NPV = .64). CONCLUSION: The K-T cancellation test showed a good diagnostic performance in discriminating cognitively normal older adults from cognitively impaired patients. Our findings support the clinical utility of K-T in geriatric neuropsychological assessment for detection of early cognitive impairment.

Normative values for carotid intima media thickness and its progression: Are they transferrable outside of their cohort of origin?

BACKGROUND: The clinical use of carotid intima media thickness (cIMT) requires normal values, which may be subject to variation of geographical factors, ethnicity or measurement details. The influence of these factors has rarely been studied. The aim of this study was to determine whether normative cIMT values and their association with event risk are generalizable across populations. DESIGN: Meta-analysis of individual participant data. METHOD: From 22 general population cohorts from Europe, North America and Asia we selected subjects free of cardiovascular disease. Percentiles of cIMT and cIMT progression were assessed separately for every cohort. Cox proportional hazards models for vascular events were used to estimate hazard ratios for cIMT in each cohort. The estimates were pooled across Europe, North America and Asia, with random effects meta-analysis. The influence of geography, ethnicity and ultrasound protocols on cIMT values and on the hazard ratios was examined by meta-regression. RESULTS: Geographical factors, ethnicity and the ultrasound protocol had influence neither on the percentiles of cIMT and its progression, nor on the hazard ratios of cIMT for vascular events. Heterogeneity for percentiles of cIMT and cIMT progression was too large to create meaningful normative values. CONCLUSIONS: The distribution of cIMT values is too heterogeneous to define universal or regional population reference values. CIMT values vary widely between different studies regardless of ethnicity, geographic location and ultrasound protocol. Prediction of vascular events with cIMT values was more consistent across all cohorts, ethnicities and regions.

Inflammatory markers and extent and progression of early atherosclerosis: Meta-analysis of individual-participant-data from 20 prospective studies of the PROG-IMT collaboration.

BACKGROUND: Large-scale epidemiological evidence on the role of inflammation in early atherosclerosis, assessed by carotid ultrasound, is lacking. We aimed to quantify cross-sectional and longitudinal associations of inflammatory markers with common-carotid-artery intima-media thickness (CCA-IMT) in the general population. METHODS: Information on high-sensitivity C-reactive protein, fibrinogen, leucocyte count and CCA-IMT was available in 20 prospective cohort studies of the PROG-IMT collaboration involving 49,097 participants free of pre-existing cardiovascular disease. Estimates of associations were calculated within each study and then combined using random-effects meta-analyses. RESULTS: Mean baseline CCA-IMT amounted to 0.74 mm (SD = 0.18) and mean CCA-IMT progression over a mean of 3.9 years to 0.011 mm/year (SD = 0.039). Cross-sectional analyses showed positive linear associations between inflammatory markers and baseline CCA-IMT. After adjustment for traditional cardiovascular risk factors, mean differences in baseline CCA-IMT per one-SD higher inflammatory marker were: 0.0082 mm for high-sensitivity C-reactive protein (p < 0.001); 0.0072 mm for fibrinogen (p < 0.001); and 0.0025 mm for leucocyte count (p = 0.033). 'Inflammatory load', defined as the number of elevated inflammatory markers (i.e. in upper two quintiles), showed a positive linear association with baseline CCA-IMT (p < 0.001). Longitudinal associations of baseline inflammatory markers and changes therein with CCA-IMT progression were null or at most weak. Participants with the highest 'inflammatory load' had a greater CCA-IMT progression (p = 0.015). CONCLUSION: Inflammation was independently associated with CCA-IMT cross-sectionally. The lack of clear associations with CCA-IMT progression may be explained by imprecision in its assessment within a limited time period. Our findings for 'inflammatory load' suggest important combined effects of the three inflammatory markers on early atherosclerosis.

[Carotid atherosclerosis and dementia]. / Athérosclérose carotidienne et démences.

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.

A novel device for measuring arterial stiffness using finger-toe pulse wave velocity: Validation study of the pOpmètre®.

BACKGROUND: The finger-toe pathway could be a good alternative for assessing arterial stiffness conveniently. AIM: To evaluate the accuracy of the pOpmètre®--a new device that measures finger-toe pulse wave velocity (ft-PWV). METHODS: The pOpmètre has two photodiode sensors, positioned on the finger and the toe. Pulse waves are recorded continuously for 20 seconds, and the difference in pulse wave transit time between toe and finger (ft-TT) is calculated. The travelled distance is estimated using subject height. Study 1 compared ft-PWV with carotid-femoral PWV (cf-PWV) obtained by the reference method (SphygmoCor®) in 86 subjects (mean age 53±20 years), including 69 patients with various pathologies and 17 healthy normotensives. Study 2 compared changes in ft-PWV and cf-PWV during a cold pressor test in 10 healthy subjects. Study 3 assessed repeatability in 45 patients. RESULTS: ft-PWV correlated significantly with cf-PWV (R2=0.43; P<0.0001). A better correlation was found in terms of transit time (R2=0.61; P<0.0001). The discrepancy between transit times was related to age. The cold pressor test induced parallel changes in cf-PWV and ft-PWV, with increased aortic stiffness that was reversible during recovery. Intra-session repeatability was very good, with a coefficient of variation of 4.52%. CONCLUSION: The pOpmètre® allows measurement of arterial stiffness in routine clinical practice. The greatest advantages of ft-PWV are simplicity, rapidity, feasibility, acceptability by patients and correct agreement with the reference technique. Further studies are needed to adjust for bias and to validate the pOpmètre in larger populations.

Carotid intima-media thickness progression and risk of vascular events in people with diabetes: results from the PROG-IMT collaboration.

OBJECTIVE: Carotid intima-media thickness (CIMT) is a marker of subclinical organ damage and predicts cardiovascular disease (CVD) events in the general population. It has also been associated with vascular risk in people with diabetes. However, the association of CIMT change in repeated examinations with subsequent CVD events is uncertain, and its use as a surrogate end point in clinical trials is controversial. We aimed at determining the relation of CIMT change to CVD events in people with diabetes. RESEARCH DESIGN AND METHODS: In a comprehensive meta-analysis of individual participant data, we collated data from 3,902 adults (age 33-92 years) with type 2 diabetes from 21 population-based cohorts. We calculated the hazard ratio (HR) per standard deviation (SD) difference in mean common carotid artery intima-media thickness (CCA-IMT) or in CCA-IMT progression, both calculated from two examinations on average 3.6 years apart, for each cohort, and combined the estimates with random-effects meta-analysis. RESULTS: Average mean CCA-IMT ranged from 0.72 to 0.97 mm across cohorts in people with diabetes. The HR of CVD events was 1.22 (95% CI 1.12-1.33) per SD difference in mean CCA-IMT, after adjustment for age, sex, and cardiometabolic risk factors. Average mean CCA-IMT progression in people with diabetes ranged between -0.09 and 0.04 mm/year. The HR per SD difference in mean CCA-IMT progression was 0.99 (0.91-1.08). CONCLUSIONS: Despite reproducing the association between CIMT level and vascular risk in subjects with diabetes, we did not find an association between CIMT change and vascular risk. These results do not support the use of CIMT progression as a surrogate end point in clinical trials in people with diabetes.

A web-based program for informal caregivers of persons with Alzheimer's disease: an iterative user-centered design.

BACKGROUND: Web-based programs have been developed for informal caregivers of people with Alzheimer's disease (PWAD). However, these programs can prove difficult to adopt, especially for older people, who are less familiar with the Internet than other populations. Despite the fundamental role of usability testing in promoting caregivers' correct use and adoption of these programs, to our knowledge, this is the first study describing this process before evaluating a program for caregivers of PWAD in a randomized clinical trial. OBJECTIVE: The objective of the study was to describe the development process of a fully automated Web-based program for caregivers of PWAD, aiming to reduce caregivers' stress, and based on the user-centered design approach. METHODS: There were 49 participants (12 health care professionals, 6 caregivers, and 31 healthy older adults) that were involved in a double iterative design allowing for the adaptation of program content and for the enhancement of website usability. This process included three component parts: (1) project team workshops, (2) a proof of concept, and (3) two usability tests. The usability tests were based on a mixed methodology using behavioral analysis, semistructured interviews, and a usability questionnaire. RESULTS: The user-centered design approach provided valuable guidelines to adapt the content and design of the program, and to improve website usability. The professionals, caregivers (mainly spouses), and older adults considered that our project met the needs of isolated caregivers. Participants underlined that contact between caregivers would be desirable. During usability observations, the mistakes of users were also due to ergonomics issues from Internet browsers and computer interfaces. Moreover, negative self-stereotyping was evidenced, when comparing interviews and results of behavioral analysis. CONCLUSIONS: Face-to-face psycho-educational programs may be used as a basis for Web-based programs. Nevertheless, a user-centered design approach involving targeted users (or their representatives) remains crucial for their correct use and adoption. For future user-centered design studies, we recommend to involve end-users from preconception stages, using a mixed research method in usability evaluations, and implementing pilot studies to evaluate acceptability and feasibility of programs.

Gender-specific trends in heart rate in the general population from 1992-2007: a study of 226,288 French adults.

OBJECTIVES: Heart rate (HR) has been associated with cardiovascular (CV) risk factors and with CV mortality. Trends in CV risk factors have been described in recent decades, but HR changes over time have been less studied. We thus aimed to examine the secular trends in HR and interrelationships between HR and traditional CV risk factors and mortality. METHODS: We studied 226,288 consecutive participants (141,533 men and 84,755 women) aged 44.7 ± 12.7 years who had a free standard health check up, between 1992 and 2007. Each had resting HR measured systematically on a 10-cycle electrocardiogram, and assessment of lipoproteins, blood pressure, smoking, glycemic status, body mass index, and physical activity. Sex-specific trends in mean HR were estimated by a general linear model adjusted for traditional CV risk factors and CV treatment. In that model, year was considered as a continuous variable. RESULTS: Crude mean HR decreased over the study period (from 68.9 ± 10.4 to 63.7 ± 9.0 beats/min in men; from 72.2 ± 10.3 to 65.2 ± 9.0 beats/min in women; p < 0.001 for both). The amplitude of the HR decrease was similar after full adjustment and across the pre-cited risk factors categories. On multivariate analysis, higher HR (≥ 80 beats/min vs. <60 beats/min) was associated with higher mortality rate over 5 years in men (hazard ratio 2.11, 95% CI 1.79-2.49) and women (hazard ratio 1.58, 95% CI 1.16-2.15). CONCLUSION: In this large population-based study of 226,288 middle-aged participants, heart rate declined over 16 years independently of traditional CV risk factors.

Home blood pressure measurement in elderly patients with cognitive impairment: comparison of agreement between relative-measured blood pressure and automated blood pressure measurement.

OBJECTIVES: Home blood pressure measurement (HBPM) is recommended by guidelines for hypertension management. However, this method might be difficult to use in elderly individuals with cognitive disorders. Our aim was to assess the agreement and the feasibility of HBPM by a relative as compared with 24-h ambulatory blood pressure monitoring (ABPM) in elderly patients with dementia. METHODS: Sixty outpatients with dementia aged 75 years and older with office hypertension (≥140/90 mmHg) were subjected successively to HBPM by a trained relative and 24-h ABPM. The order of the two methods was randomized. Current guidelines' thresholds for the diagnosis of hypertension were used. RESULTS: The mean (SD) age of the patients was 80.8 (6.1) years (55% women) and the mean (SD) mini-mental state examination score was 20.1 (6.9). The feasibility of relative-HBPM was very high, with a 97% success rate (defined by ≥12/18 measurements reported). The blood pressure measurements were highly correlated between the two methods (r=0.75 and 0.64 for systolic blood pressure and diastolic blood pressure, respectively; P<0.001 for both). The agreement between the methods for the diagnosis of sustained hypertension and white-coat hypertension was excellent (overall agreement, 92%; κ coefficient, 0.81; 95% CI, 0.61-0.93). Similar results were found for daytime-ABPM. CONCLUSION: In cognitively impaired elderly patients, HBPM by a relative using an automated device was a good alternative to 24-h ABPM.

Use of vitamin K antagonist therapy in geriatrics: a French national survey from the French Society of Geriatrics and Gerontology (SFGG).

OBJECTIVE: We aimed to evaluate the quality and determinants of vitamin K antagonists (VKA) control among very elderly patients in geriatric settings. METHODS: A national cross-sectional survey was conducted among patients aged ≥80 years who were hospitalized in rehabilitation care or institutionalized in a nursing home and who were treated by VKA. Time in therapeutic range (TTR) was computed according to Rosendaal's method. RESULTS: A total of 2,633 patients were included. Mean [± standard deviation (SD)] age was 87.2 ± 4.4 years and 72.9 % were women. The main indication for VKA therapy was atrial fibrillation (AF; 71.4 %). Mean (±SD) TTR was 57.9 ± 40.4 %. After backward logistic regression, poorer VKA control (TTR <50 vs. ≥50 %) was associated with being hospitalized in rehabilitation care [odds ratio (OR)(rehab. vs. nursing home) = 1.41; 95 % CI 1.11-1.80], the indication for VKA treatment (OR(prosthetic heart valve vs. AF) = 4.76; 95 % CI 2.83-8.02), a recent VKA prescription (OR(<1 vs. >12 months) = 1.70; 95 % CI 1.08-2.67), the type of VKA (OR(fluindione vs. warfarin) = 1.22; 95 % CI 1.00-1.49), a history of international normalized ratio >4.5 (OR = 1.50; 95 % CI 1.21-1.84), a history of major bleeding (OR = 1.88; 95 % CI 1.00-3.53), antibiotic use (OR = 1.83; 95 % CI 1.24-2.70), and falls (OR(≥2 falls during the past year vs. <2) = 1.26; 95 % CI 1.01-1.56). CONCLUSION: Overall, VKA control remains insufficient in very old patients. Poorer VKA control was associated with taking VKA for a prosthetic heart valve, a recent VKA prescription, the use of other VKAs than warfarin, a history of overcoagulation and major bleeding, antibiotic use, and falls.