EVA Study Research Articles

Plasma Carotenoid Levels and Cognitive Performance in an Elderly Population: Results of the EVA Study

The hypothesis of carotenoids having a preventive role in cognitive impairment is suggested by their antioxidant properties. We examined, in a cross-sectional analysis, the relationship between cognitive performance (assessed by the Mini-Mental State Examination, Trail Making Test Part B, Digit Symbol Substitution, Finger Tapping Test, and Word Fluency Test) and different plasma carotenoids (lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene, and trans-beta-carotene and cis-beta-carotene) in a healthy elderly population (the EVA,"Etude du Vieillissement Artériel," study; n = 589, age = 73.5 +/- 3 years). Logistic regression showed that participants with the lowest cognitive functioning (<25th percentile) had a higher probability of having low levels of specific plasma carotenoids (<1st quartile): lycopene and zeaxanthin. For zeaxanthin, odds ratios (ORs) were as follows: OR(DSS) = 1.97 (95% confidence interval [CI] = 1.21-3.20), OR(FTT) = 1.70 (CI = 1.05-2.74), and OR(WFT) = 1.82 (CI = 1.08-3.07); for lycopene, OR(DSS) = 1.93 (CI = 1.20-3.12) and OR(TMTB) = 1.64 (CI = 1.04-2.59). Even if it is not possible to affirm if these low levels of carotenoids precede or are the consequence of cognitive impairment, our results suggest that low carotenoid levels could play a role in cognitive impairment. The biological significance of our findings needs further research.

Selenium and Mortality in the Elderly: Results From the EVA Study

Selenium and Mortality in the Elderly: Results From the EVA Study

P1-199: Selenium evolution and cognitive decline in the elderly: Results from the EVA study

P1-199: Selenium evolution and cognitive decline in the elderly: Results from the EVA study

Polymorphism R92Q of the tumour necrosis factor receptor 1 gene is associated with myocardial infarction and carotid intima-media thickness--the ECTIM, AXA, EVA and GENIC Studies.

The TNFRSF1A gene was screened for polymorphisms in 95 subjects with premature myocardial infarction (MI), who also had one parent who had an MI. A total of 10 polymorphisms were found: three in the promoter region, two in exons and five in introns. All polymorphisms were genotyped in ECTIM, a case-control study of MI (1815 subjects). The nonsynonymous 92Q allele was found in 1.8, 1.0 and 1.7% of controls from Strasbourg, Belfast and Glasgow - respectively; in cases: 4.2, 2.2 and 3.2%. The population-adjusted odds ratio (OR) for MI associated with allele Q carrying was 2.15 (95% CI: 1.09-4.23). To check its possible implication in atherosclerosis, this polymorphism was then genotyped in the AXA Study (ultrasound examinations of carotid and femoral arteries in the context of an employment medical examination, 733 subjects), the EVA Study (ultrasound examinations of carotid arteries in a study of cognitive and vascular ageing, 1092 subjects) and the GENIC Study (on brain infarction (BI), 912 subjects). In the AXA Study, among smokers, carrying the 92Q allele was positively associated with the presence of a carotid plaque (OR 5.07; 95% CI: 1.64-15.63) and with a thickening of the carotid intima-media thickness (IMT) (0.59 (0.11) vs 0.54 (0.11), P=0.045). In the EVA Study, carriers of allele 92Q had an increased mean carotid IMT (0.70 (0.09) vs 0.67 (0.13), P=0.02). No significant association of the 92Q allele was found with BI in the GENIC Study. Overall, these results may suggest that carriers of the 92Q allele may be at increased risk of atherosclerosis.

Effects of lipid peroxidation and antioxidant status on peak flow in a population aged 59–71 years: the EVA study

Oxidative stress is implicated in age-related diseases and is a possible determinant in the loss of lung function. The aim of our study was to examine the association between blood indicators of oxidative metabolism and lung function in an old population. The relationships of three antioxidant indicators (selenium, total carotenoids and α-tocopherol) and of a marker of lipid peroxidation (thiobarbituric acid-reactive substances (TBARs)) with age and height-adjusted PEF were assessed in 688 subjects aged 59–71 years (61% never smokers, 30% ex-smokers, 9% current smokers). Stratified analyses according to gender and smoking were performed. Gender, age, tobacco and alcohol consumption, educational level and body mass index were taken into account as potential confounders. Regarding antioxidant markers, PEF was significantly positively associated with total carotenoids in the whole group ( P=0.03), and with selenium among ex-smokers only ( P=0.008). Regarding lipid peroxidation, PEF was significantly negatively associated with TBARs in men only ( P=0.02). Consistent results were observed when analyzing quantitative values and quartiles of biological markers. Results are consistent with the hypothesis of the role of both oxidants and antioxidants on lung function in elderly. Research is needed to better understand the effect of former smoking in the surviving elderly subjects.

Longitudinal Study of Carotid Atherosclerosis and White Matter Hyperintensities: The EVA-MRI Cohort

Background and Purpose: White matter hyperintensities (WMHs) are often observed on cerebral magnetic resonance imaging (MRI) of elderly individuals. Epidemiological studies have shown that age and hypertension are associated with WMHs, suggesting a vascular mechanism in WMH pathogenesis. In a population-based prospective study, we examined the association of carotid atherosclerosis measured at baseline and 4-year follow-up with severity of WMHs assessed at 4-year follow-up. Methods: The sample consisted of 640 healthy subjects aged 59–71 years at entry enrolled in the prospective EVA Study. Systolic and diastolic blood pressures were measured at each wave. Ultrasonographic measures of intima-media thickness (IMT) of the common carotid arteries and plaques were made at baseline and at 4-year follow-up examination. An MRI examination was performed at 4-year follow-up. The presence and severity of WMHs were evaluated by a single radiologist. Results: After adjusting for age, gender, and hypertension, the presence of carotid plaques at baseline was significantly associated with the presence of severe WMHs 4 years later [odds ratio (OR) = 1.70; 95% confidence interval (CI): 1.05–2.74]. The association was stronger in men than in women. A 0.1-mm increase of baseline IMT was associated with an increased risk of severe WMHs in both sexes (adjusted OR = 1.17; 95% CI: 0.96–1.41), but the association was not significant (p = 0.12). Cross-sectional relationships between carotid plaques and severe WMHs at 4-year follow-up showed that the risk of having severe WMHs was stronger in the group of subjects who had already plaques at study entry compared to the group of subjects whose plaques occurred during 4-year follow-up. Conclusion: This study confirmed an association between carotid atherosclerosis and WMHs independently of age and hypertension. It also suggested that the older the carotid plaques, the higher the risk of having severe WMHs.

Les études épidémiologiques sur le vieillissement en France : de l’étude Paquid à l’étude des Trois Cités

Follow-up of cohorts recruited in general population with active screening and diagnosis of incident cases, is the most appropriate epidemiological design for studying incidence and risk factors of Alzheimer disease and other types of dementia. In France, people considered in the PAQUID study, then in the EVA study, have been the first cohorts on dementia. They have prepared the way for the Three-City (3C) study, conducted in Bordeaux, Dijon and Montpellier. About 9500 persons aged 65 years and over have been recruited in these three cities and will be followed-up during four years. The main objective of the 3C study is to investigate the relation between vascular risk and neurodegenerative diseases. The 3C study will provide essential data for defining strategies for dementia prevention. To measure the impact of the strategies on the incidence of dementia and the social burden of this disease will be an important public health objective in the near future.

Association of postmenopausal hormone replacement therapy with carotid atherosclerosis and soluble thrombomodulin: The vascular aging (EVA) study

Hormone replacement therapy (HRT) may reduce atherosclerosis among postmenopausal women, partly by reducing vascular endothelium damage. We have tested this hypothesis by evaluating the association of HRT with firstly, carotid intima media thickness (IMT) and plaques, and secondly, with endothelial cell damage, indicated by soluble thrombomodulin (sTM). Then, we tested the association between the two markers of atherosclerosis and the levels of sTM. Among 747 postmenopausal women included into the EVA study, we compared 154 HRT users (including 80% transdermal treatment) with 593 never users. Carotid IMT and plaques were measured with B-mode ultrasonography and sTM with ELISA. At least one plaque was detected among 13.6% of HRT users and 27.3% of never users. After adjustment for confounding factors, the odds ratio for the presence of plaque was 0.45 (95% confidence interval, 0.25–0.78, P=0.005) in HRT users in comparison with nonusers. HRT users had a slightly lower crude mean IMT than nonusers, but the difference was not significant. sTM was positively associated with mean IMT ( P for trend=0.001) but not with plaques. Finally, estrogen users had a lower sTM level than nonusers (difference 0.14 ng/ml, P=0.03). As HRT was associated with sTM and plaques, but not with IMT, while sTM was only associated with IMT, our hypothesis was not confirmed. This suggests that the possible beneficial effects of HRT on atherosclerosis may not go through the endothelial cell damage assessed by plasma thrombomodulin.

Oxidative stress, enzymatic activities and cognitive decline in the EVA study

L’objectif de cette étude est de proposer des normes en population générale pour les fluences verbales catégorielles (couleurs, animaux, fruits, villes) et littérales (lettres « L » et « P »).Cette étude a été réalisée à partir des données de la cohorte PAQUID, une cohorte prospective en population générale conduite dans les départements de la Gironde et de la Dordogne.Le sous-échantillon analysé a porté sur 1730 personnes, non institutionnalisées et non démentes, vues au suivi à cinq ans de la cohorte. Les normes ont été calculées en fonction de l’âge (70–74 ans, 75–79 ans, ≥ 80 ans), du niveau d’études (pas de scolarité, niveau primaire ou secondaire court et au moins secondaire court validé) et du sexe. Pour chaque épreuve, le nombre de bons mots produits ainsi que le nombre de répétitions ont été calculés.Les épreuves de fluence verbale étant classiquement utilisées dans l’examen des fonctions cognitives de sujets présentant une atteinte cérébrale focale ou une pathologie neurodégénérative, les normes présentées dans cette étude pourront intéresser les cliniciens pour situer les performances de leurs patients âgés de 70 ans et plus par rapport à ceux de sujets âgés normaux.Verbal fluency tasks are frequently used in neuropsychological examinations. The aim of this study was to produce norms for a normal elderly population in semantic (colors, animals, fruits, city names) and letter fluency (letters “L” and “P”) tasks performed in 60 seconds.These data were collected as part of the PAQUID cohort, a French population-based study on aging conducted in Gironde and Dordogne.The sub-sample analyzed included 1730 non-institutionalized and non-demented subjects. Norms were calculated according to age (70–74 years, 75–79 years, ≥80 years), sex and educational level (no diploma, primary degree, secondary degree and higher). For each task, the number of correct words produced and repetition errors were analyzed.The contribution of this work is to provide clinicians with normative scores for semantic and letter fluency tasks helpful for interpreting the performances of elderly patients consulting for cognitive disorders.

Risk of dementia in parents of probands with and without the apolipoprotein E4 allele. The EVA study.

STUDY OBJECTIVE: Age, family history of dementia and the epsilon 4 allele of the apolipoprotein E gene have been associated with Alzheimer's disease (AD). Considering the strength of APOE-epsilon 4...

Cross-sectional and 4-year longitudinal associations between brachial pulse pressure and common carotid intima-media thickness in a general population. The EVA study.

The cross-sectional and 4-year longitudinal associations between brachial pulse pressure (PP) and ultrasound measurements of common carotid intima-media thickness (CCA-IMT) were assessed. A population of 957 volunteers aged 59 to 71 years was recruited from the electoral rolls of the city of Nantes (western France) and reexamined 4 years later. Longitudinal changes in PP and CCA-IMT were computed as the difference between 4-year follow-up and baseline values. Baseline CCA-IMT and PP were positively associated in both age- and sex-adjusted analysis (partial correlation coefficient=0.20, P<0.001) and in multivariate analysis adjusted for traditional cardiovascular risk factors and mean blood pressure (partial correlation coefficient=0.18, P<0.001). In longitudinal analysis, baseline PP was associated with the change in 4-year CCA-IMT (partial correlation coefficient=0.11, P<0.001), and baseline CCA-IMT was a predictor of the 4-year change in PP (partial correlation coefficient=0.10, 0.001<P<0.01). No association between mean blood pressure and CCA-IMT was observed once PP was taken into account, in either cross-sectional or longitudinal analyses (partial correlation coefficients ranged from 0.00 to 0.03). Similar patterns of results were observed in hypertensive, nonhypertensive, and antihypertensive-treated and -nontreated subjects. This longitudinal study of a large population of relatively aged subjects suggests that elevated levels of PP are associated with the progression of CCA-IMT, and increased CCA-IMT is associated with PP widening. The nature of these relationships and whether atherosclerosis progression over time is involved or not in these associations merit further investigations.

Polymorphism of the prion protein is associated with cognitive impairment in the elderly: the EVA study.

Little is known about the role of the prion protein (PrP(sen)/gene PRNP). PRNP knockout mice studies suggest that PrP(sen) may be involved in CNS degeneration. This observation prompted us to examine the influence of PRNP genetic variability on cognitive abilities in the elderly. In a community-based sample of 1,163 subjects aged 59 to 71 years, we characterized the valine (Val) and methionine (Met) allele of the PRNP polymorphism at codon 129. The effect of this polymorphism was estimated on the Mini-Mental State Examination (MMSE) and on a global composite score built from a battery of nine different neuropsychological tests. The results were adjusted for age, gender, education, and apolipoprotein E (apoE) polymorphism. Cognitive impairment (MMSE score < 24) was present in 2.5% of the Met-Met individuals, 2.9% of the Met-Val individuals, and 7.0% of Val-Val subjects (p = 0.02). Subjects homozygous for the PRNP Val allele had a lower MMSE and global score than the two other genotypes (p < 0.003). This effect was of the same magnitude as that of the apoE epsilon4 allele on cognitive performances. Both apoE epsilon4 and PRNP Val allelic effects were additive. This observation suggests that variability of the PRNP locus may be associated with cognitive performance in the elderly. This result, if confirmed, offers potential clues for the role of PRNP in the human brain.

Systemic Oxidative Stress and Cognitive Performance in the Population-Based EVA Study

The aim of this study was to examine the relationships between cognitive functioning and blood levels of antioxidants and lipoperoxidation products in an elderly population. In 1991–1992, 1389 volunteers (574 men and 815 women aged 59 to 71 years) were recruited from the general population. Levels of selenium, carotenoids, and thiobarbituric-reactive substances in plasma and of vitamin E, glutathione peroxidase, and Cu-Zn superoxide dismutase in red blood cells were measured. Cognitive functioning was assessed with various psychometric tests. We used logistic regression to estimate the risk of poor cognitive functioning (<25th percentile of the score distribution) associated with low values of each antioxidants (<25th percentile) including potential confounding factors. A low level of total carotenoids (<1.86 μmol/l) was associated with poor cognitive performance in two tests assessing visual attention and logical reasoning: the Trail-Making Test part B [OR = 1.34 IC95% (0.99–1.81), p = .055] and the Digit Symbol Substitution from the WAIS-R [OR = 1.38 IC95% (1.02–1.89), p = .04]. Low levels of other antioxidants and high levels of thiobarbituric-reactive substances were not related to poor cognitive functioning. Results observed with plasma carotenoids are in accordance with previous data obtained mostly from dietary records.

Cardiovascular determinants of plasma fibronectin in an elderly population

Plasma fibronectin was determined in 1262 individuals (742 females, 520 males) aged 59-71 years at the beginning of an epidemiological study on vascular aging (the EVA study) in Nantes, western France. The average values (62.88+/-20.30 mg/100 ml for males, n=520 and 62.15+/-18.85 mg/100 ml for females, n=742) and the distribution of values were comparable for males and females. Significant positive correlations were found in both sexes between plasma fibronectin values and some cardiovascular risk factors such as body mass index, systolic and diastolic blood pressure, total and low density lipoprotein (LDL)-cholesterol, apolipoprotein B, triglycerides and fibrinogen. A significant negative correlation was found with high density lipoprotein (HDL)-cholesterol. No correlation was found between fibronectin values and smoking or alcohol consumption. Multiple regression analysis showed that systolic blood pressure, LDL cholesterol and triglycerides remained significantly associated with plasma fibronectin whereas only marginal associations were found with age, body mass index and fibrinogen. These results are in agreement with previous findings showing a strong increase in fibronectin in atherosclerotic plaques and also the complex formation between fibronectin and LDL. These results substantiate the claim that modifications of the metabolism of extracellular matrix components accompany the atherosclerotic process.

Aging of the vascular wall: serum concentration of elastin peptides and elastase inhibitors in relation to cardiovascular risk factors. The EVA study

The relations of biological markers of extracellular matrix (plasma elastin peptides and elastase inhibitors) to the clinical history of cardiovascular diseases and risk factors for atherosclerosis were examined in a large population study (the EVA Study) on vascular and cognitive aging performed in 1389 men and women aged 59–71 years. A moderate decrease in elastin peptides was observed in women with a self-reported history of coronary heart disease ( P<0.091) and stroke ( P<0.03) as well as with diabetes ( P<0.043). Similar but non-significant trends were found in men. Furthermore, elastin peptides were significantly and positively correlated to HDL-cholesterol and apolipoprotein A1 in both sexes. On the other hand, elastase inhibitor titers were significantly higher in women than in men. A moderate increase was also found in men ( P<0.097) and women ( P<0.068) with a history of coronary heart disease that reached significance level after pooling both sexes ( P<0.014). Furthermore, elastase inhibitor titers were significantly and positively related to fibrinogen and C reactive protein in either sex. No consistent associations were observed between both biological markers of extracellular matrix and age, blood pressure, body mass index and tobacco or alcohol consumption. These results suggest that a decrease in elastin peptides and an increase in elastase inhibitors might be associated with risk factors of atherogenesis as well as with atherosclerosis-related diseases.

Combined effects of lipid peroxidation and antioxidant status on carotid atherosclerosis in a population aged 59ߝ71 y: The EVA Study. Etude sur le Vieillisement Artériel

There are few epidemiologic studies of the effects of lipid peroxidation and antioxidant status on atherosclerosis. The relation of lipid peroxidation evaluated by thiobarbituric acid-reactive substances (TBARS) and biological markers of antioxidant status to ultrasonographically assessed carotid atherosclerosis was examined from baseline data of a longitudinal study on cognitive and vascular aging (Etude sur le Vieillisement Artériel, the EVA Study). The study sample was composed of 1187 mean and women aged 59-71 y without any history of coronary artery disease or stroke. Ultrasound examination included measurements of intima-media thickness (IMT) on the common carotid arteries (CCAs) and at the site of plaques. After adjustment for conventional cardiovascular risk factors, erythrocyte vitamin E was significantly and negatively associated with CCA-IMT in both men and women whereas plasma selenium and carotenoids were not. No association was found between TBARS and CCA-IMT in either sex. However, TBARS were significantly higher in men with carotid plaques than in those without. This association was strengthened in men with concentrations of erythrocyte vitamin E, plasma selenium, and carotenoids below the lowest quartile. Our findings give some epidemiologic support to the hypothesis that lipid peroxidation and low antioxidant status are involved in the early phases of atherosclerosis.

Breathing disorders during sleep and cognitive performance in an older community sample: the EVA Study.

To determine whether poor cognitive performance was associated with symptoms related to the sleep apnea syndrome, snoring, and breathing stoppage during sleep. Cross-sectional analysis of data collected at baseline in the EVA Study, a 4-year cohort study. The city of Nantes in western France. A total of 1389 persons, aged 60 to 70 years, recruited from the electoral rolls of the city of Nantes. Demographic characteristics and data on drug use and tobacco and alcohol consumption were collected using a standardized questionnaire. Weight and height were measured. Individuals completed a previously validated sleep questionnaire about nocturnal sleep characteristics, snoring, breathing stoppage during sleep, and day-time sleepiness. Trained psychologists administered eight neuropsychological tests: The Mini-Mental State Examination, Trail Making Test, Digit Symbol Substitution Test of the WAIS-Revised, Benton Visual Retention Test, Paced Auditory Serial-Addition Task, Auditory Verbal Learning Test, Raven Progressive Matrices, and Word Fluency Test. Depressive symptomatology was assessed by the Center for Epidemiologic Studies-Depression scale. In this older sample, 49.5% of subjects reported snoring, and 10.8% reported breathing stoppage during sleep. Both respiratory disorders were associated significantly with male gender and high body mass index. In men, prevalence of snoring was increased significantly in those with alcohol consumption greater than 40 mL per day. Breathing stoppage during sleep was associated with depressive symptoms in women. Logistic regression models adjusted for age, gender, educational level, tobacco status and alcohol consumption, depressive symptomatology, and number of medications found that both snoring and breathing stoppage were associated with low scores (< or = 10th percentile) in tests requiring visual attention skills, the Trail Making Test (OR = 2.14, 95% CI = 1.24-3.69 and OR = 1.88, 95% CI = 1.04-3.39, respectively), and the Digit Symbol Substitution Test (OR = 1.80, 95% CI = 1.09-2.99 and OR = 1.58, 95% CI = .87-2.89, respectively). These relationships were significant only when either snoring or breathing stoppage was associated with daytime sleepiness. This cross-sectional analysis suggested that in community-dwelling individuals 60 to 70 years of age, snoring and breathing stoppage during sleep associated with daytime sleepiness were risk factors for low cognitive performance in tests requiring visual attention skills.

Early effect of ApoE-ε4 allele on cognitive results in a group of highly performing subjects: the EVA study

Early effect of ApoE-ε4 allele on cognitive results in a group of highly performing subjects: the EVA study

Early effect of ApoE-ϵ4 allele on cognitive results in a group of highly performing subjects: the EVA study

We examined the association between apolipoprotein E (ApoE) ϵ4 allele and cognitive performances in a population sample of 1174 high functioning volunteers aged 59–71 years. The neuropsychological battery included the Mini Mental State Examination (MMSE) and nine tests assessing visual attention, verbal memory, visual processing, logical reasoning, psychomotor rapidity, visual memory, auditory attention and verbal fluency. The ratio of genotypes with zero, one or two ϵ4 alleles was 70.6%, 21.4% and 1.9%, respectively. The ϵ4 allele was significantly associated with lower scores for visual attention, psychomotor rapidity and MMSE. In the best performer subgroup (MMSE score above 25, n = 1028), all relationships persisted. Our findings demonstrate that the ApoE-ϵ4 allele is early associated with low normal cognitive performances in areas which are not specifically affected at the subclinical onset of dementia.

Ultrasonographic assessment of carotid wall characteristics and cognitive functions in a community sample of 59- to 71-year-olds. The EVA Study Group.

This study was aimed at analyzing cross-sectional relationships between cognitive performance and ultrasonographic assessment of carotid wall characteristics. A cohort of 1279 subjects (men, 41%) aged 59 to 71 years was recruited from the electoral rolls of the city of Nantes (western France). Cognitive performances were evaluated with the Mini-Mental State Examination (MMSE) and seven neuropsychological tests assessing attention, psychomotor rapidity, verbal abilities, memory, and visuospatial perception. For each test, subjects were classified into three performance levels with a quartile distribution: 25% highest, 25% lowest, and 50% middle. The intima-media thickness of common carotid arteries and the presence of plaques in the carotid arteries were assessed with B-mode ultrasound examination. Only 28% of men and 17% of women had carotid plaques inducing moderate stenosis of the lumen ( < 40%). After adjustment for possible confounders, odds ratios for poor cognitive performance associated with plaques were above 1 for all cognitive tests in men. This association was statistically significant for the MMSE and another test assessing attention skills. There was a slight association between increase of the common carotid intima-media thickness and poor cognitive scores in men with plaques. In women, no association was found between cognitive functions and presence of plaques or intima-media thickness. This study indicated a moderate association between atherosclerosis of the carotid arteries and poor cognitive functioning in men aged 59 to 71 years. In view of these moderate cross-sectional results, further studies are required to better assess the relationship between carotid atherosclerosis and cognitive impairment.