Flavie ; Letois

Thibault Mura

Jacqueline Scali

Laure-Anne Gutierrez

Catherine Feart

Dr Claudine Berr
email: claudine.berr@inserm.fr

Catherine Féart

Nutrition and mortality in the elderly over 10 years of follow-up: the Three-City study

Keywords: mortality, dietary habits, fruits and vegetables, olive oil, fish mortality, dietary habits, fruits and vegetables, olive oil, regular fish consumption

niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Abstract

In the last 20 years, many prospective cohort studies assessed the relationships between food consumption and mortality. Result interpretation is mainly hindered by the limited adjustment for confounders and, to a lesser extent, the small sample sizes. The aim of this study was to investigate the association between dietary habits and all-cause mortality in a multicentre prospective cohort that included non-institutionalized community-based elderly individuals (3-City Study). A brief Food Frequency Questionnaire was administered at baseline. Hazard ratios (HRs) and 95% confidence intervals (95%CIs) for all-cause mortality were estimated relative to the consumption frequency of several food groups, using Cox proportional hazards models adjusted for sex, centre, socio-demographic characteristics and health status indicators. Among the 8937 participants (mean age: 74.2 y, 60.7% women), 2016 deaths were recorded during an average follow-up of nine years.

The risk of death was significantly lower among subjects with the highest fruit and vegetable consumption (HR=0.90, 95%CI=0.82-0.99, p=0.03) and with regular fish consumption (HR=0.89, 95%CI=0.81-0.97, p=0.01). The benefit of olive oil use was found only in women (moderate olive oil use: HR=0.80, 95%CI=0.68-0.94, p=0.007; intensive use: HR=0.72, 95%CI=0.60-0.85, p=0.0002). Conversely, daily meat consumption increased the mortality risk (HR=1.12, 95%CI=1.01-1.24, p=0.03). No association was found between risk of death and diet diversity, use of various fats. These findings suggest that fruits/vegetables, olive oil and regular fish consumption have a beneficial effect on the risk of death, independently of the sociodemographic features and the number of medical conditions.

Introduction

The number of elderly people is progressively increasing. Besides medical progress, the life expectancy increase could be linked also to environmental and behavioural factors, some of which can be modified to achieve beneficial effects for health, particularly dietary habits [START_REF] King | Turning back the clock: adopting a healthy lifestyle in middle age[END_REF] . The importance of diet has led public health policy-makers to develop specific prevention programmes. Moreover, large observational studies have examined the relationship between diet and all-cause mortality in elderly subjects using various food habit classifications that focus, for example, on specific foods or food consumption groups, or dietary patterns that combine multiple features. They showed that some dietary patterns (eating habits, including several food groups), such as the Mediterranean diet (2; 3; 4; 5; 6; 7; 8; 9; 10; 11; 12; 13) , or "healthy" dietary groups defined by high consumption of fruits and vegetables and fish (14; 15; 16; 17) , or greater consumption of olive oil with raw vegetables [START_REF] Masala | A dietary pattern rich in olive oil and raw vegetables is associated with lower mortality in Italian elderly subjects[END_REF] , have a protective effect. Similarly, some studies on consumption frequency found that high intake of fruits and/or vegetables (19; 20; 21) , fish (20; 22) or coffee (23; 24; 25) has a beneficial effect on survival. However, few of these studies have considered the most relevant adjustment factors. Indeed, dietary habits and mortality are both influenced by many factors not only at the individual level (age, sex, health status, socio-economic, cultural and genetic factors), but also at the population level (for instance, food availability and accessibility in terms of cost).

Another way to assess the effect of diet on health is to consider the concept of food diversity. The advantage of studying the diversity of diets and of used fats compared with monotonous diets is that this allows evaluating the consumption of the most essential micronutrients and of different types of fatty acids (FA). This concept is part of the French National Health and Nutrition Programme [START_REF]French National Nutrition and Health Program[END_REF] . Indeed, a varied diet, defined by the daily consumption of at least one unit of each essential food group, has been associated with a lower mortality risk (27; 28) . However, few studies have focused on this approach. Therefore, our main objective was to examine the associations between dietary habits and mortality in an elderly population. The data collected by the 10-year follow-up study of the large French population-based Three-City (3C) cohort allowed investigating whether some dietary habits (consumption of fruits, vegetables, olive oil, fish and caffeine, diet diversity and diversity of used

Methods

Data were extracted from the database of the 3C study, a prospective cohort study of vascular risk factors of dementia [START_REF]Vascular factors and risk of dementia: design of the Three-City Study and baseline characteristics of the study population[END_REF] . The present study was conducted according to the Declaration of Helsinki guidelines. The 3C study protocol was approved by the Consultative Committee for the Protection of Persons participating in Biomedical Research of the Kremlin-Bicêtre University Hospital (Paris, France). All participants signed a written informed consent.

Participants

A sample of community dwellers aged 65 years and older was selected in 1999-2000 from the electoral rolls of Bordeaux (South-West of France), Montpellier (South-East of France) and Dijon (North-East of France). To be eligible for recruitment into the study [START_REF]Vascular factors and risk of dementia: design of the Three-City Study and baseline characteristics of the study population[END_REF] , persons had to be (1) living in these cities or their suburbs and registered on the electoral rolls, (2) aged 65 years and over, and

(3) not institutionalized. The cohort size by center was set at 2,500 in Bordeaux, 5,000 in Dijon and 2,500 in Montpellier. A personal letter was sent to each potential subject inviting them to participate and including a brief description of the study protocol and an acceptance/refusal form. The spouse/partner was also invited to participate in the study if he/she met eligibility criteria. As electoral rolls are occasionally inaccurate (persons who have moved may still be registered at their previous address), no further correspondence was sent to persons who did not respond to the first letter, but an attempt was made to contact them by telephone.Twenty-four percent of the eligible persons selected on the electoral rolls (n = 34,922) could not be reached; among those contacted, the acceptance rate was 37%.A total of 9,693 persons were included; 7 persons aged less than 65 years were subsequently excluded. Participants who had subsequently refused to participate in the baseline medical interview (n = 392) were excluded from all analyses leading to an original sample of 9294 community dwellers.

The participants were administered standardized questionnaires and underwent clinical examinations at baseline and after 2, 4, 8 and 10 years. Baseline data were collected by standardized face-to-face interview. They included information on sociodemographic features, lifestyle (including a brief Food Frequency Questionnaire), current symptoms and complaints, medical For the current study, the following participants were excluded: 132 (1.4%) subjects with missing data for at least one dietary variable, 214 (2.3%) people with a diagnosis of dementia at baseline, and 11 (0.12%) individuals with no available vital statistics data. The analysis was thus carried out using a sample of 8,937 participants with a mean follow-up of 8.85 years.

Baseline dietary assessment

The brief Food Frequency Questionnaire (FFQ) was administered at baseline to assess the participants' dietary habits concerning nine broad food categories: (1) meat and poultry, (2) fish (including seafood), (3) eggs, (4) milk and dairy products, (5) cereals (including bread and starches), (6) raw fruits, (7) raw vegetables, (8) cooked fruits or vegetables, and (9) pulses.

Consumption frequency was classified as follows: never, less than once per week, once per week, 2-3 times per week, 4-6 times per week and daily. The dietary habits of the whole sample have been described previously [START_REF] Larrieu | Sociodemographic differences in dietary habits in a population-based sample of elderly subjects: the 3C study[END_REF] . Participants were also invited to indicate the dietary fats used at least once per week for dressing, cooking, or spreading among those included in the following list: butter, margarine, maize oil, peanut oil, sunflower or grapeseed oil, olive oil, blended oil, duck or goose fat, lard, 'Vegetaline'© (mainly saturated fat), colza oil, walnut oil, soybean oil. Caffeine consumption was calculated by multiplying the number of tea and coffee cups drunk per day by their estimated caffeine content (about 50mg/cup for tea and 100mg/cup for coffee, respectively) (31) .

Fruits/vegetables, fish, meat and olive oil were the four main food consumption groups of interest that were studied as categorical variables. Their consumption thresholds were based on the French National Nutrition and Health Programme guidelines, when applicable to the available data (26) . Cooked fruits and vegetables, olive oil and caffeine consumption were investigated using previously defined categories (31; 32; 33) . Dietary habits included the intake of fish/seafood (less than twice per week versus more than twice a week), fruits and vegetables (less than one fruit and one vegetable, cooked or raw, per day versus at least one fruit and one vegetable, cooked or raw, per day, and less versus more than 4-6 servings of cooked fruits or vegetables per week), meat (less versus more than once per day), caffeine (<250mg/day, 250-375mg/day, >375mg/day). Three categories of olive oil consumption were defined: 'no use', 'moderate use' (for cooking or dressing alone), or 'intensive use' (for cooking and for dressing) (32; 34) . To calculate the Diet Diversity Score (DDS) (from 0 to 5), one point was assigned for each of the following food categories consumed at least once per day: dairy products, meat, cereals, fruits and vegetables. Low diversity was defined by a DDS <3 and high diversity by a DDS ≥4 [START_REF] Kant | Dietary diversity and subsequent cause-specific mortality in the NHANES I epidemiologic follow-up study[END_REF] . Fat diversity was evaluated as ≤3 different fats versus >3 fats. The threshold of three different fats corresponds to the median value of various fats used by the population included in the 3C cohort.

Baseline covariates

Socio-demographic information recorded at baseline included age, sex, centre, educational level (no or primary/middle/high school/university), occupation (white collar, employee, blue collar, housewife) and monthly income level (<1,500, >1,500 euros). Health behaviours were assessed based on smoking status (no, 0-10, 10-30 or >30 packets per year), intake of alcoholic beverages (0-24g/day, >24g/day for women; 0-36g/day, >36g/day for men).

Blood pressure and anthropometric data were measured in standardized conditions. Healthrelated variables included body mass index (BMI: <27 and ≥27kg/m 2 ) [START_REF] Heiat | An evidence-based assessment of federal guidelines for overweight and obesity as they apply to elderly persons[END_REF] , hypertension (defined as a systolic blood pressure >140mm Hg or diastolic blood pressure >90mm Hg, or use of antihypertensive drugs) [START_REF] Brindel | Prevalence, awareness, treatment, and control of hypertension in the elderly: the Three City study[END_REF] , diabetes (fasting blood glucose ≥7.0 mmol/l, or taking an anti-diabetic treatment), hypercholesterolemia (yes/no, self-reported) and the number of drugs (0, 1-4, ≥ 5).

History of cardiovascular diseases (yes/no) and other chronic diseases (chronic respiratory disease, cancer, Parkinson's disease or hypothyroidism) were reported. Disability was estimated using the Instrumental Activities of Daily Living scale (IADL; yes (score>0/no,). Depressive mood was assessed using the Center for Epidemiological Studies-Depression scale (CES-D) and was defined by a score <17 for men and <23 for women. Self-rated health was grouped in three categories (poor, average, fair) and self-assessment of correct diet in two classes (no /yes).

Physical activity was assessed differently in the three centres (self-reported or not and with different accuracy levels). Therefore, a common binary variable was considered for the three centres (none or low/regular). Regular physical activity was defined as doing some sport regularly or having at least one hour of leisure or household activity per day [START_REF] Feart | Adherence to a Mediterranean diet and risk of fractures in French older persons[END_REF] . Given the important amount of missing data for this variable (1115 missing data for the Bordeaux centre, 11% of the whole sample), it was used only in sensitivity analyses.

Vital status

Mortality was ascertained from the civil registry by systematic request for all subjects not included in follow-up visits. The date of death was defined as the date of event and the date of the last follow-up or phone contact for the 10-year follow-up as the date of censoring. Follow-up included the precise assessment of all causes of death that were coded according to the tenth revision of the International Classification of Diseases (ICD-10) [START_REF] Alperovitch | Do we really know the cause of death of the very old? Comparison between official mortality statistics and cohort study classification[END_REF] . Mortality from cardiovascular disease (CVD) (ICD-10: I) and cancer (ICD-10: C), the two leading causes of death in aged populations, were considered for the analyses [START_REF] Alperovitch | Do we really know the cause of death of the very old? Comparison between official mortality statistics and cohort study classification[END_REF] .

Statistical Analyses

Survival analysis was carried out using the Kaplan Meier method. Comparisons of baseline characteristics and dietary habits were performed with the log-rank test.

The associations between dietary habits, diet diversity and mortality risk were determined by using Cox proportional hazards regression with delayed entry, with age (in years) used as the time axis and left truncation at the age of study entry. The results of the survival analysis were expressed as hazard ratios (HRs) with 95% confidence intervals (CI).

In these analyses, the adjustments for covariates were performed in three steps. Univariate analysis was the basic model to test associations between dietary features and mortality (crude model). The second model (model 1) was adjusted for sex and study centre, educational level, occupation and income. Health behaviours and health factors, chosen based on literature data, were then added in the third model (model 2). Interactions between the different dietary habits and covariates included in model 2 were tested and stratified analyses were carried out accordingly.

For missing data, multiple imputations were used by generating five copies of the original dataset in which the missing values for the covariates considered in the analysis were replaced by values generated according to the Markov Chain Monte Carlo (MCMC) method and using the PROC MI procedure. Each imputed dataset was analysed as if it were complete to calculate the mean HRs and CI with the PROC MIANALYZE procedure [START_REF] Yuan | Multiple Imputation Using SAS Software[END_REF] . Imputation were performed for covariates included in analyses: education (missing data 0.17%), income (6.13%), occupation (0.29%), smoking (1.63%), alcohol (1.51%), history of cardiovascular disease (0.08%), , depression (1.28%), diabetes (5.65%), hypertension (0.06%), hypercholesterolemia (1.1%), dependence ( 0.69%)self-rated health (0.57%), number of chronic diseases (0.09%), self rated diet quality (2.38%).

Analyses were carried out using the SAS software (version 9.2).

Results

The baseline characteristics and dietary habits of the participants (n=8937) according to their vital status (dead/alive) at the end of the 10-year follow-up are reported in Table 1 andTable 2, respectively.Participants who died (n=2016) were significantly older at baseline than those still alive (mean age: 77 vs 73, respectively) and more often men, heavy smoker or alcohol consumers.

They also had more often a history of cardiovascular or chronic diseases, more vascular risk factors and poor self-rated health. In these crude comparisons, mortality risk was higher among individuals with low income and blue collar workers. Conversely, survival was not influenced by the education level in this highly educated population. Daily consumption of fruits and vegetables, regular consumption of cooked vegetables/fruits, intensive olive oil use, wide fat diversity and bi-weekly fish consumption were more frequently reported by subjects still alive at the end of the 10-year follow-up. Caffeine consumption and DDS were not associated with survival.

Then, the associations between the 10-year mortality risk and dietary habits or diet diversity (at baseline) were assessed after multiple imputations for missing data (Table 3 andTable 4, respectively). In crude analyses, various well-known healthy food habits were significantly associated with better survival: eating at least one fruit and one vegetable (raw or cooked) per day, consumption of at least four cooked fruit/vegetable servings per week, fish at least twice per week, meat less than once per day, greater diet diversity and diversity in fat use.

In the partly (only sociodemographic covariates) and fully (sociodemographic and healthrelated covariates) adjusted models, consuming at least one fruit and vegetable per day and consuming more than four cooked fruit/vegetable servings per week remained significantly associated with a better survival compared with lower levels of consumption (HR=0.90, 95% CI=0.82-0.99, p=0.03 and HR=0.80, 95% CI=0.70-0.90, p=0.0005, respectively, in the fully adjusted models). Fish intake at least twice per week was also significantly associated with better survival (HR=0.89, 95% CI=0.81-0.97, p=0.01), while consuming meat more than once per day had a deleterious effect on survival in the fully adjusted models (HR=1.12, 95% CI=1.01-1.24, p=0.03) (Table 3).

For the two indicators of diet diversity (DDS and diversity in fats used), the significant associations observed in crude and partly adjusted analyses were no longer significant after adjustment also for health-related variables (Table 4). As the interaction between sex and consumption of olive oil was significant, analyses were stratified by sex (Supplementary Table 1). The use of olive oil was inversely correlated with the mortality risk after adjustment for all covariates, but only in women (moderate olive oil use: HR=0.80, 95%CI=0.68-0.94, p=0.007; intensive use: HR=0.72, 95%CI=0.60-0.85, p=0.0002). Furthermore, sensitivity analyses were performed on the 5322 individuals with available data on physical activity. In this sub-sample, the consumption of at least 4-6 servings of cooked fruits or vegetables per week was again associated with a lower mortality risk at the end of the 10year follow-up, independently of physical activity (HR=0.75, 95% CI=0.62-0.90, p=0.002). No association was observed between mortality risk and meat, fish or olive oil consumption (Supplementary Table 2) or diet diversity (Supplementary Table 3).

Finally, there was no significant association between dietary habits/diversity and the main causes of death (389 due to CVD and 542 to cancer) after controlling for sex, centre, educational level, income and occupation (data not shown).

Discussion

The present study based on the 10-year follow-up of a French cohort of people aged 65 or older suggests that healthy dietary habits, such as daily consumption of fruits and vegetables, eating fish twice per week and regular use of olive oil (this only in women), are linked to better survival, independently of sociodemographic, health-related and lifestyle variables. Overall, higher diet diversity also is significantly associated with lower mortality risk.

A major difficulty when assessing food habits concerns the heterogeneity of the collected data. Indeed, each country has its consumption standards, tailored to cultural habits and the local availability of food resources. Moreover, the methods used to collect such data also are not homogeneous and consequently results are difficult to compare and generalize from one country to another. Nevertheless, the various eating habits can be standardized in dietary patterns (such as composite scores or consumption patterns of some preferred foods) or by quantitative measurements of food types. Studies on diet quality or adherence to a particular diet are used to determine the most beneficial approach; however, in the case of composite scores, the proper role of each score component cannot be identified. In the present study where food habits were evaluated with a short FFQ, we examined food groups that have been found to be associated with longer lifespan in previous studies using these different approaches. Our results are in agreement with the French National Nutrition and Health Programme guidelines that include the promotion of daily consumption of fruit and vegetables [START_REF]French National Nutrition and Health Program[END_REF] .

We observed a significant association between high consumption of fruits and vegetables and survival after adjusting for major confounders. This result is consistent with earlier studies (19; 20; 21) . In the EPIC study, a better adherence to a plant-based diet was associated with a reduced mortality risk in Southern Europe, but not in the UK nor in Germany, after controlling for all known risk factors [START_REF] Bamia | Dietary patterns and survival of older Europeans: the EPIC-Elderly Study (European Prospective Investigation into Cancer and Nutrition)[END_REF] . Similarly, the "Olive oil and salad" pattern was associated with longevity in an Italian elderly cohort [START_REF] Masala | A dietary pattern rich in olive oil and raw vegetables is associated with lower mortality in Italian elderly subjects[END_REF] . Fruits and vegetables, which were not separate entities in our FFQ, are the main source of antioxidants that are the basis of the free radical theory of ageing [START_REF] Harman | Free radical theory of aging: dietary implications[END_REF] . According to this theory, a balance between free radicals and antioxidants increases life expectancy. Some authors hypothesize that plant foods promote the activation of immune functions or have protective properties (16; 17) . A recent literature review highlighted the effect of high concentration of polyphenols, carotenoids, folic acid and vitamin C on mortality [START_REF] Chrysohoou | Longevity and diet. Myth or pragmatism?[END_REF] . High consumption of flavonoids, found mainly in fruits, could be associated with reduced mortality risk [START_REF] Ivey | Flavonoid intake and all-cause mortality[END_REF] . The beneficial effects of fruits and vegetables could be also explained by their fibre content that modulates LDL cholesterol level, insulin sensitivity and blood pressure [START_REF] Streppel | Dietary fiber intake in relation to coronary heart disease and all-cause mortality over 40 y: the Zutphen Study[END_REF] , all conditions associated with increased mortality risk. This hypothesis is supported by the PREDIMED study that demonstrated a significant association between lower risk of death and baseline higher fibre intake and fruit consumption [START_REF] Buil-Cosiales | Fiber intake and all-cause mortality in the Prevencion con Dieta Mediterranea (PREDIMED) study[END_REF] .

Our results are in agreement with the few studies that investigated fish consumption and risk of death (20; 22) . A Japanese study found that high consumption of vegetables and fish in subjects older than 75 years is associated with better survival [START_REF] Iimuro | Dietary pattern and mortality in Japanese elderly patients with type 2 diabetes mellitus: does a vegetable-and fish-rich diet improve mortality? An explanatory study[END_REF] . Most of the published results on the positive association between fish and lower mortality have been carried out in countries with traditional high fish consumption (Japan and Scandinavia). Other studies included fish consumption in the diet scores (e.g., the Mediterranean Diet Score) or in "healthy" diet patterns (14; 16; 45) with contrasting results. Hoffman et al. did not find any significant association between these dietary patterns and mortality [START_REF] Hoffmann | Comparison of two statistical approaches to predict allcause mortality by dietary patterns in German elderly subjects[END_REF] . Conversely, Anderson et al [START_REF] Anderson | Dietary patterns and survival of older adults[END_REF] observed a positive link between survival and a healthy dietary pattern (consumption of low-fat dairy products, fruit, whole grains, poultry, fish and vegetables). The protective effect of fish consumption on health has been linked to the antiinflammatory effects of the essential omega-3 fatty acids (13; 22) .

Olive oil is the main source of fat in the traditional Mediterranean diet. Our study reported a beneficial effect only among women. This finding is in agreement with the findings in an elderly British cohort [START_REF] Hamer | Dietary patterns, assessed from a weighed food record, and survival among elderly participants from the United Kingdom[END_REF] where the Mediterranean style dietary pattern was associated with reduced mortality only in women. This sex-specific effect could be explained by the women's longer life expectancy. Many studies support the beneficial effect of the Mediterranean diet on mortality (2; 3; 4; 5; 6; 7; 8; 12; 46) . Masala et al. observed that the 'Olive Oil & Salad' dietary pattern (high consumption of olive oil) is inversely associated with all-cause mortality in the elderly [START_REF] Masala | A dietary pattern rich in olive oil and raw vegetables is associated with lower mortality in Italian elderly subjects[END_REF] . The PREDIMED study found that higher consumption of olive oil was associated with a specific reduction in the cardiovascular mortality risk in an elderly Mediterranean population [START_REF] Guasch-Ferre | Olive oil intake and risk of cardiovascular disease and mortality in the PREDIMED Study[END_REF] . The beneficial effect of olive oil could be explained by its high concentration in mono-unsaturated fatty acids and phenolic compounds that improves endothelium function and reduces oxidative stress, thereby promoting healthy aging and longevity [START_REF] Chrysohoou | Longevity and diet. Myth or pragmatism?[END_REF] .

On the other hand, we found that daily consumption of meat, as a broad category, had a negative effect on survival. Most previous studies showing a deleterious effect of meat consumption on lifespan (17; 45) also found that high meat consumption patterns were often associated with unhealthy dietary habits, such as high levels of fat consumption. However, in other studies, red meat consumption was not associated with increased mortality risk after correction for confounding [START_REF] Anderson | Dietary patterns and survival of older adults[END_REF] . Comparisons with previous findings are limited by the different definitions of meat consumption groups. In some works red meat with high content of fatty acids was considered on its own, whereas poultry or lean meat was not included in the analysis. Anderson et al. suggested that high consumption of animal foods could increase the mortality risk, only if meat replaces protective plant foods in the diet [START_REF] Anderson | Dietary patterns and survival of older adults[END_REF] . The link between red meat and dietary fat could affect the lipid and lipoprotein profile and thus the cardiovascular disease risk [START_REF] Hoffmann | Comparison of two statistical approaches to predict allcause mortality by dietary patterns in German elderly subjects[END_REF] .

The association between diet diversity and mortality did not remain significant after adjustment for confounders, unlike in other studies (27; 28) . However, comparisons are difficult because these studies used different methods of food collections and different food groups.

The data from our study should be interpreted in the light of the following limitations. First, the 3C sample is not representative of the French population. Indeed, compared with the whole French population, this cohort included more urban dwellers, in better health and living together [START_REF] Larrieu | Sociodemographic differences in dietary habits in a population-based sample of elderly subjects: the 3C study[END_REF] . Therefore, extrapolation of our results to the general population of elderly should be made with caution. The FFQ did not record quantitative data (portions, grams), but only frequencies of consumption. Low frequency consumption does not necessarily mean lower energy intake, but simply suggests a lack of diversity in eating habits. Moreover, the FFQ did not allow calculating the total energy intake, as recommended to better control for confounding factors and to reduce extraneous variation [START_REF] Willett | Adjustment for total energy intake in epidemiologic studies[END_REF] . In a previous article exclusively on the population from the Bordeaux centre (N=1660) of the 3C study, daily energy intake was calculated in a sub-sample by using the 24-hour dietary recall technique. In this sub-sample, daily energy intake was not affected by the frequency of consumption of fish, or of fruits and vegetable (frequent vs less frequent), or by the use of omega-3 or omega-6 rich oils (regular vs non-regular) [START_REF] Barberger-Gateau | Dietary patterns and risk of dementia: the Three-City cohort study[END_REF] . Moreover, the baseline energy intake among the Bordeaux sub-sample was not significantly different between those who were dead (N=375) or still alive (N=1422) at the end of the 10-year follow-up (data not shown). This suggests that the energy intake is not a major confounder in the present analyses. According to the literature, mainly studies with the most accurate data on food consumption (in daily amount) (3; 7; 15; 16; 18; 20; 21; 22; 43; 46) found significant associations between dietary patterns and mortality. Our data did not allow this level of detail. However, our results confirm the benefit of several food categories on survival. Moreover, in our study, the assessment of dietary intake covered only broad food groups. This limitation is important for the interpretation of the association between meat and survival, because the meat group included both white meat (lean, healthy) and red meat (fat, deleterious). The limitations the food questionnaire (FFQ) used in this study (few items, absence of validation, only baseline administration) could have led to non-differential misclassification bias. However, previous studies using this questionnaire reported innovative results that are in agreement with the literature or have been successively confirmed by other independent analyses (30; 34; 49; 50) . Finally in our sensitivity analysis including physical activity, only the association with fruits and vegetables remains significant. But the variable physical activity did not rely on a detailed physical activities questionnaire and these analyzes are conducted in a limited sample (n=5273) reducing statistical power. The interpretation of this result is therefore limited.

Strengths of this study include the prospective population-based study design, with a large sample size, the completeness of the collected dietary data (data provided by more than 99% of subjects, possibly due to the use of a simple and short questionnaire) and the low number of dropouts (0.1%). Many variables were investigated as potential confounders, such as socio-demographic factors, health behaviours, BMI, drug use, self-rated health status and diet. The FFQ used in the 3C study has already allowed highlighting many interesting associations between diet habits and diseases (31; 33; 34; 49; 50; 51; 52; 53) . Chrysohoou et al. insisted on the importance of taking into account socio-economic factors when considering the relationship between food habits and life expectancy, as healthy habits are associated with financial and educational status [START_REF] Chrysohoou | Longevity and diet. Myth or pragmatism?[END_REF] . In our study, we considered simultaneously education, occupation and income.

In conclusion, this study on the associations between dietary habits and mortality in a large population-based elderly cohort brings reliable evidence that could be used for developing nutritional programmes. Specifically, a diet with a daily intake of fruits and vegetables, regular consumption of fish, as recommended by the French Nutrition and Health Programme [START_REF]French National Nutrition and Health Program[END_REF] , and regular use of olive oil promotes longevity among an elderly community-living population. Diet quality is an important component of a healthy lifestyle that has beneficial effects on survival [START_REF] King | Turning back the clock: adopting a healthy lifestyle in middle age[END_REF] .

Additional studies should investigate the association between survival, diet and healthy behaviours, but this does not limit the importance of this simple public health message.

  associated with reduced all-cause mortality in people aged >65 years, independently of previously identified major confounders.

  pressure, past and present consumption of tobacco, alcohol and drug use, anthropometric data, neuropsychological testing and blood sampling.

Table 1 -Baseline socio-demographic and medical characteristics of the 3C cohort (N=8937) subdivided according to their vital status (dead or alive) at the end of the 10-year follow-up

 1 Coronary heart disease was reported by 671 (9.7%) of subjects alive and 398 (20%) of subjects dead at the end of the follow-up.bAssessed with the IADL scale (at least 1 impairment). c Chronic diseases included mainly respiratory diseases and dyspnoea (n=477, 5.8% of people still alive; n=285, 14.1% of subjects dead at the end of the follow-up), Parkinson's disease (n=46, 0.66% of alive; n=59, 2.9% of dead subjects), and hyperthyroidism (n=6, 18 9% of alive; n=143, 7.1% of dead).

	Alive N=6921 (77%)	Dead N=2016 (23%)
	N (%)	mean (sd)	N (%)	mean (sd)

a

Table 2 -Baseline food habits of the 3C cohort (N=8937) subdivided according to their vital 401 status (alive or dead) at the end of the 10-year follow-up

 2

	402
		Alive N=6921 (77%)	Dead N=2016 (23%)
		N (%)	N (%)
	At least 1 fruit and 1 vegetable, cooked or raw /day 2782 (40%)	663 (33%)
	Cooked fruits/vegetables: ≥4-6 servings/week	6162 (89%)	1715 (85%)
	Meat: ≥1 serving/day	1689 (24%)	558 (28%)
	Fish: ≥2 servings/week	3569 (52%)	923 (46%)
	Diversity diet score ≥4	4986 (72%)	1371 (68%)
	Olive oil use
	None	1543 (23%)	644 (32%)
	Moderate	2768 (40%)	755 (37%)
	Intensive	2610 (38%)	617 (31%)
	Different fats >3	1523 (22%)	345 (17%)
	Caffeine (mg/day)
	<250	4781 (69%)	1489 (74%)
	250-375	1441 (21%)	370 (18%)
	>375	699 (10%)	157 (8%)
	Self-rated diet quality
	Bad	589 (9%)	171 (9%)
	Good	6174 (91%)	1790 (91%)

Page 18 of 26 Cambridge University Press British Journal of Nutrition F o r R e v i e w O n l y 19Table 3 -Association between 10-year overall mortality and dietary habits in the 3C elderly cohort (N=8937): crude and adjusted hazard ratios (HR) and 95% CI

 3 Cox proportional model adjusted for sex, centre, education, income, occupation and also smoking, alcohol consumption, history of cardiovascular diseases, BMI, depression, diabetes, hypertension, hypercholesterolemia, dependence (IADL scale), self-rated health, self-rated diet quality, number of drugs, number of chronic diseases.

				N	Crude	(95% CI)	p	Model 1 a (95% CI)	p	Model 2 b (95% CI)	p
	At least 1 fruit and 1 vegetable, cooked	8937 0.82	[0.75-0.90]	*** 0.84	[0.77-0.93]	*** 0.90	[0.82-0.99] *
	or raw/day
	Cooked fruits or vegetables: ≥4-6/ week 8937 0.73	[0.65-0.83]	*** 0.78	[0.69-0.89]	*** 0.80	[0.70-0.90] ***
	Meat: ≥1 serving/day			8937 1.22	[1.11-1.34]	*** 1.16	[1.05-1.28]	**	1.12	[1.01-1.24] *
	Fish: ≥2 servings/week	F o F o F o	8937 0.83	[0.76-0.91]	*** 0.87	[0.80-0.96]	**	0.89	[0.81-0.97] **
			r r r
	*P<0.05; **P<0.01; ***P<0.001	R e v i e w R e v i e w R e v i e w
						O n O n O n
							l y l y l y

a Cox proportional model adjusted for sex, centre, education (no or primary/secondary/ high school/university), income (<1500 or >1500 euros/month), occupation (white collar/employee/blue collar/housewife) b

British Journal of Nutrition

Cambridge University PressBritish Journal of Nutrition

Acknowledgments

The 3C Study was conducted under a partnership agreement between the Institut National de la Santé et de la Recherche Médicale (INSERM), the Victor Segalen -Bordeaux II University and the Sanofi-Synthélabo Company. The Fondation pour la Recherche Médicale supported the preparation and initiation of the study. The 3C Study is also supported by the Caisse Nationale Maladie des Travailleurs Salariés, Direction Générale de la Santé, Conseils Régionaux of Aquitaine, Languedoc-Roussillon and Bourgogne, Fondation de France, Ministry of Research-INSERM Programme 'Cohortes et collections de données biologiques', Mutuelle Générale de l'Education Nationale, Institut de la longévité, Conseil Général de la Côte d'Or, Agence Nationale de la Recherche ANR PNRA 2006 and Longvie 2007 and Fonds de coopération scientifique Alzheimer (FCS 2009-2012).

Conflict of interest

None for F Letois, T Mura, J Scali, LA Gutierrez,C Berr.

C Féart received fees for conferences from Danone Research and Nutricia.

Authorship


Thibault Mura

Hélène Amieva

Marcel Goldberg

Jean-François Dartigues

Joel Ankri

Marie Zins

Claudine Berr

Effect size for the main cognitive function determinants in a large cross-sectional study

établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Original Article: «Effect size» for the main cognitive function determinants in a large cross-sectional study.

Thibault Mura 1,2,8 , Hélène Amieva 3,4 , Marcel Goldberg 1,5 , Jean-François Dartigues 6 , Joël Ankri 7 , Marie Zins 1,5 , Claudine Berr 2,8 .

(1) Population-based Epidemiological Cohorts Unit, UMS 011 Inserm-UVSQ, Villejuif, France and Versailles Saint Quentin en Yvelines University, Versailles, France The study of age-related cognitive decline has become a major public health challenge due to the ageing of the European population and the expected increase in the prevalence of dementia in the coming years [START_REF] Mura | How many dementia cases in France and Europe? Alternative projections and scenarios 2010-2050[END_REF][START_REF] Singh-Manoux | The importance of cognitive aging for understanding dementia[END_REF]. The gradual onset of cognitive impairment is a characteristic sign of most dementias, including Alzheimer's disease. It is now accepted that dementia and cognitive impairment are the result of a pathophysiological process that begins many years or decades before symptom onset [START_REF] Amieva | Prodromal Alzheimer's disease: successive emergence of the clinical symptoms[END_REF][START_REF] Nelson | Neuropathology and cognitive impairment in Alzheimer disease: a complex but coherent relationship[END_REF]. Specific diagnostic criteria are therefore required, in research context, to diagnose Alzheimer's disease prior to the onset of dementia using biomarkers and neuropsychological tests [START_REF] Dubois | Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria[END_REF]. Although the assessment of cognitive abilities is routinely performed in the elderly, the wide variability of the observed performances can sometimes lead to difficulties in interpreting the results. Therefore, a good knowledge of the variables that may affect cognitive performances in a non-pathological context could facilitate the interpretation of the obtained results.

Many studies have investigated the cross-sectional association of cognitive performance with many variables, such as socio-demographic characteristics (age [START_REF] Singh-Manoux | Timing of onset of cognitive decline: results from Whitehall II prospective cohort study[END_REF][START_REF] Hedden | Insights into the ageing mind: a view from cognitive neuroscience[END_REF], sex [START_REF] Gerstorf | Stability of sex differences in cognition in advanced old age: the role of education and attrition[END_REF][START_REF] Maitland | Selective sex differences in declarative memory[END_REF][START_REF] Aartsen | Gender differences in level and change in cognitive functioning. Results from the Longitudinal Aging Study Amsterdam[END_REF] and education [START_REF] Lee | The relation of education and income to cognitive function among professional women[END_REF][START_REF] Cagney | Education, wealth, and cognitive function in later life[END_REF][START_REF] Schneeweis | Does education improve cognitive performance four decades after school completion?[END_REF][START_REF] Zahodne | Education does not slow cognitive decline with aging: 12-year evidence from the victoria longitudinal study[END_REF]), lifestyle (tobacco use [START_REF] Sabia | Smoking history and cognitive function in middle age from the Whitehall II study[END_REF], alcohol use [START_REF] Britton | Alcohol consumption and cognitive function in the Whitehall II Study[END_REF][START_REF] Elias | Alcohol consumption and cognitive performance in the Framingham Heart Study[END_REF][START_REF] Stampfer | Effects of moderate alcohol consumption on cognitive function in women[END_REF] and physical inactivity [START_REF] Singh-Manoux | Effects of physical activity on cognitive functioning in middle age: evidence from the Whitehall II prospective cohort study[END_REF][START_REF] Weuve | Physical activity, including walking, and cognitive function in older women[END_REF]), cardiovascular (diabetes mellitus [START_REF] Debling | Diabetes and cognitive function in a population-based study of elderly women and men[END_REF][START_REF] Kumari | Diabetes and cognitive function in a middle-aged cohort: findings from the Whitehall II study[END_REF][START_REF] Wu | Impact of diabetes on cognitive function among older Latinos: a population-based cohort study[END_REF] and blood pressure [START_REF] Giordano | Cognitive functions and cognitive reserve in relation to blood pressure components in a population-based cohort aged 53 to 94 years[END_REF][START_REF] Knecht | High-normal blood pressure is associated with poor cognitive performance[END_REF][START_REF] Waldstein | Nonlinear relations of blood pressure to cognitive function: the Baltimore Longitudinal Study of Aging[END_REF]) or psychological (depression [START_REF] Ganguli | Depressive symptoms and cognitive decline in late life: a prospective epidemiological study[END_REF][START_REF] Kohler | Depressive symptoms and cognitive decline in community-dwelling older adults[END_REF][START_REF] Lee | A meta-analysis of cognitive deficits in first-episode Major Depressive Disorder[END_REF][START_REF] Snyder | Major depressive disorder is associated with broad impairments on neuropsychological measures of executive function: a meta-analysis and review[END_REF]) variables. However, due to the high power of many of these studies, there may be confusion between the clinical and the statistical significance of these associations, and clinicians and/or psychologists might consider these factors as equally associated with cognitive functions. These associations are usually reported in separate papers with different methodologies, study populations, neuropsychological tests and statistical models. Moreover these studies tend to report their results using adjusted differences (beta coefficient) or odds ratio, which are inadequate to quantify "effect sizes" [START_REF] Olejnik | Measures of Effect Size for Comparative Studies: Applications, Interpretations, and Limitations[END_REF]. Thus, none of these finding allow the comparison of the effect of a given factor on several neuropsychological tests, nor of the effect of several factors on one specific neuropsychological test. To our knowledge, no analysis allowing the comparison of the «effect sizes» for the main variables influencing cognitive functions has been published yet.

Therefore, the aim of this cross-sectional study was to analyze the magnitude of associations between socio-demographic, lifestyle, cardiovascular and psychological variables and the scores of four neuropsychological tests in a 45 to 75 year-old population.

Material and methods

Study population

The "CONSTANCES" cohort [START_REF] Zins | The CONSTANCES cohort: an open epidemiological laboratory[END_REF] includes volunteers aged 18-69 years at inception who were randomly selected among French adults who are covered by the CNAMTS health insurance ("Caisse nationale d'assurance maladie des travailleurs salaries", the national health insurance of more than 85% of the French population). For this study, analyses were performed on data from participants aged 45 to 75 years who were included at one of the 17 Social Security Health Screening Centers (HSCs) involved in the "CONSTANCES" project between January 2012 and May 2014. This age range was chosen because it can be considered as the age of onset of cognitive decline [START_REF] Singh-Manoux | Timing of onset of cognitive decline: results from Whitehall II prospective cohort study[END_REF]

Socio-demographic variables

Participants were categorized in six five-year age groups. Education was categorized in seven levels according to the main stages of the French education system: no diploma (less than 5 years of education), certificate of primary or secondary education (5 to 11 years), National vocational qualifications (11 to 12 years), High School Graduation (12 to 13 years), faculty 1° or 2° cycle (14 to 15 years), first year of master degree (16 years), master degree or more (17 years of education or more)".

Lifestyle variables

Data on tobacco smoking were collected using a questionnaire on smoking status (current, past, or never).

Alcohol consumption was assessed using a questionnaire on frequency and amount of daily consumption of different alcoholic beverages (wine, beer, fortified wine, premixed spirits or cocktails) in the previous week or week-end. Alcohol consumption was classified in four categories, according to the number of alcohol units (one unit = 10-12 g of alcohol) consumed in one week: (i) abstinent (0 unit), (ii) occasional drinker (less than 7 units), (iii) moderate drinker (7 to 14 units for women, or 7 to 28 units for men) and (iv) heavy drinker (more than 14 units for women and more than 28 units for men) [START_REF]WHO. International Guide for Monitoring Alcohol Consumption and Related Harm[END_REF]34).

Physical activity was assessed using a questionnaire about frequency and duration of sports practices, regular journeys on foot or by bicycle, and repairs, gardening or household chores. Physical activity was then classified as: (i) high (2 hours/week of intensive sports practice), (ii) moderate (1 hour/week of intensive sports practice, or 2 hours/week of moderate physical activity), (iii) low (1 hour/week of moderate physical activity, or 2 hours/week of low physical activity) and (iv) very low (less than in the previous category) [START_REF] Singh-Manoux | Effects of physical activity on cognitive functioning in middle age: evidence from the Whitehall II prospective cohort study[END_REF].

Cardiovascular variables

Blood pressure was measured during the inclusion visit while lying on a bed after a 5minute rest period, using an automated oscillometric sphygmomanometer. Blood pressure was measured once on each arm and a third time (reference measure) on the arm giving the highest systolic blood pressure value. For this study, the mean value between the reference measure and the initial value on the same arm was used.

Diagnosis of diabetes mellitus was based either on self-reported diabetes (self-report questionnaire or during the medical interview), or on a fasting blood glucose concentration higher or equal to 7mmol/l.

Depressive symptomatology

Depressive symptoms were measured using the French version of the Center for Epidemiologic Studies Depression Scale (CES-D) [START_REF] Fuhrer | La version française de l'échelle CES-D (Center for Epidemiologic Studies-Depression Scale). Description et traduction de l'échelle d'autoévaluation. / The French version of the CES-D (Center for Epidemiologic Studies-Depression Scale)[END_REF][START_REF] Radloff | The CES-D Scale: A self-report depression scale for research in the general population[END_REF]. This widely-used 20-item scale evaluates the frequency and severity of the depressive symptoms experienced in the past week. The CES-D score ranges from 0 to 60 and was categorized in six classes (see Table 1).

Scores of 17 and 23 are the reference thresholds to define "possible" and "probable" cases of depression [START_REF] Husaini | Depression in rural communities: Validating the CES-D scale[END_REF].

Neuropsychological testing

The results of four neuropsychological tests were considered for the present analysis:

(1) Free and Cued Selective Reminding Test (FCSRT) [START_REF] Van Der Linden | L'épreuve de rappel libre/rappel indicé à 16 items (RL/RI -16)[END_REF][START_REF] Grober | Screening for dementia by memory testing[END_REF] to assess the verbal episodic memory. After the encoding phase (reading and memorization of 16 words, 4 by 4), the volunteer is asked to freely recall as many words as possible in two minutes. Then the neuropsychologist provides a cue (semantic category) for each word that has not been returned to help retrieving the remaining words. These free and cued recalls are repeated three times during the learning phase. The delayed recall phase takes place 20 minutes after the immediate recall and also includes free and cued recalls. For this study, both the free recall score (sum of the number of words retrieved at the three free recall trials; maximum score = 48), and the delayed free recall score (number of freely retrieved words during the delayed phase; maximum score = 16) were considered. The FCSRT total recall score (number of words retrieved by free and cued recall) and the total delayed recall score (number of words retrieved by free and cued recall at the delayed phase) were not considered because of their non-Gaussian distribution and the existence of a major ceiling effect that did not allow the use of parametric statistical methods for a reliable estimate of the «effect sizes».

(2) Verbal fluencies tasks to assess the language abilities (number of words belonging to the "animals" category named in one minute for the "semantic fluency task", and number of words starting with the letter R named in one minute for the "phonemic fluency task").

(3) Digit Symbol Substitution Task (DSST) of the Wechsler Adult Intelligence Scale-IV (WAIS-IV) [START_REF] Weschler | The Wechsler Adult Intelligence Scale-Revised[END_REF] to assess the psychomotor speed. This test includes nine digit-symbol pairs, followed by a list of numerical digits. Under each digit the subject must write the corresponding symbol as fast as possible. For this study, the number of symbols correctly associated in 90 seconds was retained. Participants must connect them in ascending order by alternating numbers and letters (e.g., 1-A-2-B-3-C ...). For this study, the (number of correct moves/total time)*10) was used.

The administration of neuropsychological tests was standardized in the 17 HSCs, with an initial and a continuous training of all neuropsychologists involved in the study. Testing practices were regularly monitored at each center.

Statistical analysis

The population's characteristics were described as proportions (categorical variables) and means ± standard deviation (continuous variables). «Effect sizes» were analyzed by computing the omega-squared coefficient (semi-partial omega-squared coefficient in SAS software) (ω2) (42) using multivariate linear regression models. Each ω2 value represents the proportion of the total variance of the neuropsychological score that is independently explained by a given variable. As this part of variance is independent, the sum of all the ω2 values of a model can be subtracted from the coefficient of determination R 2 , which quantifies the proportion of variance explained by the full model, to determine the proportion of variance shared simultaneously by several variable with the neuropsychological score (coexplained variance). The relationships between neuropsychological scores and age or education were represented graphically using adjusted means and their 95% confidence intervals. These adjusted means were computed using the same multivariate models described above. In these graphs, adjusted means between two adjacent categories were compared using Tukey's multiple comparison procedures to control for the family-wise error rate. Then, the «effect sizes» between adjacent categories were calculated using Cohen's d coefficients, based on the differences between the adjusted means of the two categories standardized by the (pooled) standard deviation of all neuropsychological test scores. We assed Multicollinearity using the variance inflation factor which had a maximum value of 1.7 after removing the variable "center of inclusion" which was collinear with the variable "neuropsychologist" because there was only one or two neuropsychologist in many centers.

Statistical analyses were performed using SAS version 9.1 (SAS Institute, Cary, North Carolina) with α = 0.05 (two-tailed tests).

Results

Among the 14,162 subjects (45 to 75-year-old) included in the cohort up to May 2014, 11,711 (83%) had complete socio-demographic, lifestyle, cardiovascular and psychological data and were retained for this study. The scores of one or more neuropsychological tests were missing for 5.7%-6.9% of participants. The participants' characteristics are detailed in Table 1.

The «effect sizes» for the different socio-demographic, lifestyle, cardiovascular and psychological variables are shown in Table 2 and in Figure 1. Overall, these variables explained from R 2 =10% (semantic fluency) to R 2 =26% (DSST) of the total variance of the neuropsychological test scores. Socio-demographic variable accounted for the greatest part of the explained variance in all tests.

The «effect size» of gender was important for the two FCSRT scores (Free Recall: ω 2 =5.2% and Delayed Free Recall: ω 2 =4.4%), moderate for the DSST (ω 2 =2.2%) and phonemic fluency task (ω 2 =0.8%) scores, and negligible or null for the semantic fluency task and TMT (A and B) scores.

Age explained independently a large part of the total variance of the DSST (ω 2 =7.5%), TMT (part A: ω 2 =7.3 and part B: ω 2 =5.9) and FCSRT (Free Recall: ω 2 =4.4% and Delayed Free Recall: ω 2 =3.1%) scores. Conversely, only a small part of the total variance of the semantic and phonemic fluency tasks was explained by age (ω 2 =0.5% and ω 2 =0.8%, respectively). Pairwise comparison of the «effect size» of successive age categories (Figure 2 and Table 3) showed that, for the DSST and the TMT-A and -B scores, the association was quite linear across all age categories. For the two FCSRT scores, the «effect sizes» increased with age. Conversely, for the phonemic and semantic fluency tasks, the association appeared only after the age of 60.

The education level was strongly correlated with all neuropsychological scores, with a large «effect size» for the DSST (ω 2 =7.2%), TMT-B (ω 2 =6.9%) and the two verbal fluency task scores (semantic fluency: ω 2 =5.8%, and phonemic fluency: ω 2 =8.9%). The «effect size» was less important for the FCSRT scores (Free Recall: ω 2 =4.7%, and Delayed Free Recall: ω 2 =2.8%) and low for the TMT-A score (ω 2 =1.4%). Pairwise comparison of the «effect size» of consecutive education levels (Figure 3 and Table 3) highlighted larger correlations for categories below senior high school), but with very little difference between subjects with 5 to 8 years and those with 9 to 11 years of education, for all neuropsychological tests. «Effect sizes» were smaller above 12-13 years of education, particularly for the DSST and the TMT scores.

A significant effect of the inclusion center was observed only for the phonemic fluency score, but with a small «effect size» (ω 2 =0.1%, p=0.03) and was thus removed from the final model to avoid collinearity with the "neuropsychologist" variable. The «effect size» of this last variable ranged from ω 2 =2.9% (TMT-A score) to ω 2 =1.2% (FCSRT Free Recall score).

The «effect sizes» of lifestyle variables were much less important than those of the socio-demographic variables (Table 2 and3). The DSST score was higher in the non-smoker group (never or former smokers) than in the smoker group. Former smokers had higher TMT-A and B scores and non-smokers had poorer results in the semantic fluency test. For all these associations, the «effect sizes» were small (respectively, ω 2 =0.18%, ω 2 =0.13%, ω 2 =0.21% and ω 2 =0.14%). Occasional alcohol consumption or abstinence was significantly associated with lower phonemic and semantic fluency task scores (ω 2 =0.28% and ω 2 =0.06%), with a possible dose effect. Finally, a high level of physical activity was associated with a better phonemic fluency task score, but with a very small «effect size» (ω 2 =0.06%).

Depressive symptomatology (CES-D score) was negatively correlated with all neuropsychological scores, but with a moderate «effect size» (from ω 2 =0.09% for the phonemic fluency task score to ω 2 =0.8% for the TMT-B).

Finally, cardiovascular variables also were associated with the cognitive performance, but with very modest «effect sizes». Systolic blood pressure between 120 and 140 mmHg was associated with better TMT-A scores (ω 2 =0.05%) and diastolic blood pressure between 70 and 80 mmHg with better FCSRT Free Recall (ω2=0.05%) and DSST scores (ω 2 =0.04%).

Diabetes was associated with poorer DSST scores (ω 2 =0.03%).

Several interactions between socio-demographic variables were tested, but were not included in the final model presented above. The interaction between age and gender was generally not significant. Only the FCSRT Free Recall and TMT-A scores showed a weaker association of age among women than men, but with a very little «effect size» (respectively, ω 2 =0.06% and ω 2 =0.11%). Interactions between age and education were not significant, except for semantic fluency (ω 2 =0.13%), but without a clear direction. The interaction between gender and education was significant for the DSST and TMT-A and -B scores with a weaker association of education among women than men, but with small «effect sizes» (respectively, ω 2 =0.24%, ω 2 =0.17% and ω 2 =0.19%).

Discussion

Our analysis based on data from a large population-based study provides reliable estimates of the «effect size» of the main cognitive function determinants. Overall, these variables explained from R 2 =10% (semantic fluency) to R 2 =26% (DSST) of the total score variance. Specifically, the socio-demographic characteristics (age, sex and education) are the main variables associated with cognitive performance variations. Conversely, lifestyle, cardiovascular variables and depressive symptoms display little association with cognitive performances ofsubjects aged 45-75 years.

The «effect size» of age was large for nearly all the tests used in the present study. The cognitive test scores decreased with age, from 50 years for most tests, but only after 60 years for phonemic fluency and 60-65 years for semantic fluency. These findings are consistent with previous cross-sectional studies that demonstrated the existence of early and significant associations of age with working memory, episodic memory and processing speed [START_REF] Hedden | Insights into the ageing mind: a view from cognitive neuroscience[END_REF][START_REF] Salthouse | Memory aging from 18 to 80. Alzheimer disease and associated disorders[END_REF]. This relationship was delayed for verbal abilities [START_REF] Hedden | Insights into the ageing mind: a view from cognitive neuroscience[END_REF], and more pronounced for phonemic than for semantic fluency [START_REF] Mathuranath | Effects of age, education and gender on verbal fluency[END_REF]. However, our cross-sectional study did not allow us to distinguish cognitive ageing from intergenerational differences, also called "cohort effect". Some authors [START_REF] Singh-Manoux | Timing of onset of cognitive decline: results from Whitehall II prospective cohort study[END_REF] have reported that cross-sectional analysis of cognitive decline with age overestimates such decline compared to longitudinal analyses. This overestimation occurred only in women because of a large difference in educational attainment between age cohorts. In this publication [START_REF] Singh-Manoux | Timing of onset of cognitive decline: results from Whitehall II prospective cohort study[END_REF], adjustment for education partially corrected this bias. In our study, women's educational attainment was comparable in all age groups and we adjusted our model for education, thus minimizing the risk of bias.

Gender was also associated with performance in most of the cognitive tests used in our study. This result is consistent with publications showing that women outperform men in tests involving verbal episodic memory (9, 10) and phonemic, but not semantic fluency [START_REF] Gerstorf | Stability of sex differences in cognition in advanced old age: the role of education and attrition[END_REF]. Our study highlights that the size of the observed association is important, with a Cohen's d value of about 0.5 for the FCSRT score, which represents a larger difference than the one observed between the 60-64 and 70-75 age groups. Gender also influenced the DSST score, consistently with previous publications [START_REF] Kaufman | Assessing adolescent and adult intelligence[END_REF].

Education was strongly associated with all neuropsychological performances, which is consistent with current knowledge. [START_REF] Lee | The relation of education and income to cognitive function among professional women[END_REF][START_REF] Cagney | Education, wealth, and cognitive function in later life[END_REF][START_REF] Schneeweis | Does education improve cognitive performance four decades after school completion?[END_REF]. In accordance with other studies, this association was more important for verbal fluency and smaller for processing speed (TMT-A) [START_REF] Zahodne | Education does not slow cognitive decline with aging: 12-year evidence from the victoria longitudinal study[END_REF]. This association was observed in all education categories, thus stressing the importance of taking into account the maximum of information when adjusting for this variable in epidemiological studies. The association between education and cognitive performances can be explained by brain development and lifelong experiences, such as lifestyle choices, health behaviors, social interactions and type of occupation [START_REF] Cagney | Education, wealth, and cognitive function in later life[END_REF][START_REF] Stern | Cognitive reserve in ageing and Alzheimer's disease[END_REF].

Our study also shows that the «effect sizes» of lifestyle variables are much smaller than those of socio-demographic characteristics. Alcohol consumption was positively correlated with phonemic and semantic fluency and with the DSST, consistently with previous works [START_REF] Britton | Alcohol consumption and cognitive function in the Whitehall II Study[END_REF][START_REF] Elias | Alcohol consumption and cognitive performance in the Framingham Heart Study[END_REF][START_REF] Stampfer | Effects of moderate alcohol consumption on cognitive function in women[END_REF]. Some authors reported a larger association for alcohol in women [START_REF] Elias | Alcohol consumption and cognitive performance in the Framingham Heart Study[END_REF][START_REF] Dufouil | Sex differences in the association between alcohol consumption and cognitive performance. EVA Study Group. Epidemiology of Vascular Aging[END_REF], not found in our study (no significant interaction between sex and alcohol consumption).

Physical activity was associated with phonemic but not with semantic fluency, as previously reported [START_REF] Singh-Manoux | Effects of physical activity on cognitive functioning in middle age: evidence from the Whitehall II prospective cohort study[END_REF]. However, these [START_REF] Singh-Manoux | Effects of physical activity on cognitive functioning in middle age: evidence from the Whitehall II prospective cohort study[END_REF] and other authors (20) also found associations with memory that we did not find in the present study, possibly because of differences in the methods used to measure physical activity intensity. Finally, tobacco consumption was associated with the performance in several cognitive tests; however, the inconstant direction of the interaction, as previously reported [START_REF] Sabia | Smoking history and cognitive function in middle age from the Whitehall II study[END_REF], makes difficult the interpretation of these results.

The «effect sizes» of cardiovascular variables were also very small. Previous publications reported a negative linear trend between blood pressure and cognitive performance [START_REF] Knecht | High-normal blood pressure is associated with poor cognitive performance[END_REF][START_REF] Kilander | Hypertension is related to cognitive impairment: a 20-year follow-up of 999 men[END_REF][START_REF] Elias | Untreated blood pressure level is inversely related to cognitive functioning: the Framingham Study[END_REF]. We did not find such a trend for any of the used neuropsychological tests, possibly because we analyzed mainly middle-aged subjects and we cannot exclude a more important effect in older people. However, our results are consistent with other works showing negative or positive associations with diastolic blood pressure, according to the studied cognitive function [START_REF] Giordano | Cognitive functions and cognitive reserve in relation to blood pressure components in a population-based cohort aged 53 to 94 years[END_REF], or non-linear correlations between blood pressure and cognitive function [START_REF] Waldstein | Nonlinear relations of blood pressure to cognitive function: the Baltimore Longitudinal Study of Aging[END_REF]. In all these studies the «effect sizes» were very small and comparable with our estimations. We also observed an association of diabetes mellitus with the DSST score and potentially with the FCSRT Free Recall score (statistical tendency). These results are consistent with studies showing the association of diabetes with global fluid intelligence [START_REF] Kumari | Diabetes and cognitive function in a middle-aged cohort: findings from the Whitehall II study[END_REF] and with attention and immediate verbal memory [START_REF] Debling | Diabetes and cognitive function in a population-based study of elderly women and men[END_REF][START_REF] Wu | Impact of diabetes on cognitive function among older Latinos: a population-based cohort study[END_REF].

The small effect size observed for lifestyle and cardiovascular variables could be partly explained by measurement errors or by the selection of particularly healthy subjects in our study. In addition, our analyses were focused mainly on a middle-aged population (from 45 to 75 years). Therefore, the small «effect size» of the cardiovascular variables, including diabetes, should not be interpreted as an absence of or a limited effect of these variables on the risk of dementia or cognitive decline in a population of older subjects.

Depressive symptomatology (CES-D score) was negatively correlated with the performance in all neuropsychological tests. This association was quite homogeneous in all tests and was not explained only by the difference in cognitive functioning between depressed and non-depressed participants. Indeed, no threshold effect (i.e., CES-D score higher than 17 for "possible" depression and 23 for "probable" depression (37)) was observed in the association between the CES-D score and the neuropsychological test performance. This association was more pronounced for tests involving executive functions (particularly the TMT-B test). This is consistent with many studies showing the association of depressive symptoms with executive functioning [START_REF] Lee | A meta-analysis of cognitive deficits in first-episode Major Depressive Disorder[END_REF][START_REF] Snyder | Major depressive disorder is associated with broad impairments on neuropsychological measures of executive function: a meta-analysis and review[END_REF]. The «effect sizes» were smaller than those reported in recent meta-analyses [START_REF] Lee | A meta-analysis of cognitive deficits in first-episode Major Depressive Disorder[END_REF][START_REF] Snyder | Major depressive disorder is associated with broad impairments on neuropsychological measures of executive function: a meta-analysis and review[END_REF], possibly because these meta-analyses included mainly case/control studies where people with major depressive disorders were compared with healthy volunteers. Conversely, cohort-based studies on the evaluation of the effect of depressive symptomatology reported «effect sizes» similar to ours [START_REF] Ganguli | Depressive symptoms and cognitive decline in late life: a prospective epidemiological study[END_REF][START_REF] Kohler | Depressive symptoms and cognitive decline in community-dwelling older adults[END_REF].

An original finding of our study is the large proportion of variance explained by the "neuropsychologist" variable, despite the high level of standardization. Its "effect size" was considerably higher than that of lifestyle, cardiovascular or psychological variables. This result emphasizes the importance of taking into account a "neuropsychologist effect" by appropriate adjustments in the analyses and/or by stratification in the study design when assessing cognition.

Our results are particularly original because we used the best adapted statistics for quantifying effect size. Indeed many studies report inadequate parameters to quantify effect sizes. Odds ratios are dependent on the threshold chosen for defining a "low cognitive level" and beta coefficients are highly dependent on the scale and the dispersion of the neuropsychological test [START_REF] Olejnik | Measures of Effect Size for Comparative Studies: Applications, Interpretations, and Limitations[END_REF]. Here, we choose omega square rather than eta square coefficient because eta square measures the variance explained of the sample, not the population, and thus always overestimates the effect size [START_REF] Maxwell | Measures of strength of association: A comparative examination[END_REF]. Further, omega square coefficient was chosen rather than partial omega square coefficient because its denominator (the total variance of the neuropsychological test) remains the same no matter which variable is being examined [START_REF] Olejnik | Measures of Effect Size for Comparative Studies: Applications, Interpretations, and Limitations[END_REF]. This makes this coefficient very interpretable for the visual representation of the level of association of these different variables.

We chose to analyze the factors which were directly and easily available, and we did not take into account some factors such as APOE4 or dietary habits. It is possible that the consideration of these factors could have change the amount of variability explained by the model (R 2 coefficient). However, it is unlikely that this would have changed estimation of effect sizes of factors already in the model."

Our study has many strengths, including its population-based design and the very large sample size that gives a high power to study variables with expected modest «effect sizes». This analysis was possible because the CONSTANCES study simultaneously collected data on many variables and on cognitive performances.

Participants of our study were selected from a data base containing over 80% of the French population. However, subjects with a low level of education (<12 years of education), smoker or diabetics were under-represented in our study compared to general statistics from France. This could be due, as in most epidemiological study, to a higher rate of participation of subject with a higher education and/or a better health. This is a limitation to the external validity of our study which can slightly affect our estimates, but with a limited impact on our interpretations and conclusions. In a general way, these "effect sizes" cannot be extrapolated to other populations in which the total variability of neuropsychological tests would be strongly different (for example older populations, with memory complaints, or with different structures of age, gender or education).

Our findings have significant clinical implications as they provide arguments to justify

what categories should be used to construct norms for each of neuropsychological tests.

Different norms for men and women should for example be used for FCRST, DDST and phonemic fluency. Regarding education, groups "5 to 11 years" and "11 to 12" years could be merged for all tests. Other levels of study could also be grouped depending on the test. It is essential to take into account age when constructing norms, although our results indicate, for example, that age groups between 45 and 60 could be merged for verbal fluencies tasks.

Conclusion

( 2 )( 4 )

 24 INSERM, U1061, Neuropsychiatrie: Recherche Epidémiologique et Clinique, 34093 Montpellier, Cedex 5, France (3) INSERM U897, Centre de Recherche en Epidémiologie et Biostatistique, Bordeaux, F-33076 France Université de Bordeaux, Bordeaux, F-33076 France (5) Université de Versailles St-Quentin, Versailles, France (6) INSERM, U897, Bordeaux, F-33076 France; Université Victor Segalen Bordeaux 2, Bordeaux, F-33076 France (7) INSERM U1168 University of Versailles St-Quentin, Sainte Perine Hospital, AP-HP, Paris, France. (8) Université Montpellier 1, Montpellier, 34093, France Corresponding author: Dr Thibault Mura, Inserm U1061 -Hôpital La Colombière, Pavillon 42, 39 av. Charles Flahault -34493 Montpellier -Cedex 5 -France Phone: 33 (0)4 67 33 23 28, Fax: 33 (0)4 67 33 23 35 email: t-mura@chu-montpellier.fr Word count: Text: 3949 Abstract: 224 Figure: 3 Table: 3 References: 49

  . The inclusion visit included a set of self-report questionnaires and a comprehensive health examination with biological sample collection. Cognitive abilities were also assessed in standardized conditions by trained neuropsychologists (33 neuropsychologists distributed among the 17 HSCs) [32]. The CONSTANCES Cohort project has obtained the authorization of the National Data Protection Authority (Commission Nationale de L'informatique et des Libertés-CNIL-#910486), and was approved by the Institutional Review Board of the National Institute for Medical Research-INSERM (#01-011).

( 4 )

 4 Parts A and B of the Trail Making Test (41) to test executive functions and shifting abilities. This test consists of 25 circles spread over a sheet of paper. In Part A, the circles are numbered from 1 to 25, and the volunteer must connect them in ascending order by drawing a line. In Part B, circles contain either a number (1 to 13) or a letter (A to L).

  Socio-demographic variables (age, gender and education) are the main variables associated with cognitive performance variations in the general 45 to 75-y-o population in France. Conversely, lifestyle, cardiovascular and psychological variables are only slightly or not associated with these performances.

Figure 1 :Figure 2 :

 12 Figure 1: Percentage of variance in the neuropsychological testing scores explained by sociodemographic, behavioral, cardiovascular and psychological variables

Figure 3 :

 3 Figure 3: Adjusted means of the neuropsychological scores according to the years of education (means with the same letter are not significantly different).

Table 1 .

 1 Characteristics of the participants

	Age (years) Age category 45-49 50-54 55-59 60-64 65-69 70-75 Gender men Years of education 17 years or more 16 years 14 to 15 years 12 to 13 years 11 to 12 years 5 to 11 years less than 5 years Smoking Never Former Current Alcohol drinking Abstinent Occasional Moderate Heavy Physical Activity Very low Low Moderate High Depressive Symptomatology CES-D 0-4 CES-D 5-10 CES-D 11-16	n 11711 2056 2184 2354 2527 2138 452 5551 1844 1042 2558 2203 2499 1225 342 5200 4977 1534 4796 2563 3175 1177 2131 3962 2052 3566 3351 3867 2369	Mean (±SD) or % 58.2 (7.2) 17.6% 18.6% 20.1% 21.6% 18.3% 3.9% 47.4 % 15.7% 8.9 % 21.8% 18.8% 21.3% 10.5% 2.9% 44.4 % 42.5 % 13.1 % 41.0 % 21.9 % 27.1 % 10.0 % 18.2 % 33.8 % 17.5 % 30.5% 28.6% 33.0% 20.2%

Table 2 :

 2 Adjusted means (±sem) of the neuropsychological testing scores and effect size (semi-partial ω2 coefficient) of socio-demographical, behavioral, cardiovascular

	factors and depressive symptomatology
	Age category	FCSRT Free recall Adjusted mean † ω2	FCSRT Delayed free recall Adjusted means † ω2	DSST Adjusted means †	ω2	Semantic Fluency Adjusted means † ω2	Phonemic Fluency Adjusted means † ω2	TMT-A Adjusted means †	ω2	TMT-B Adjusted means †	ω2
	45-49 years	33.5(0.21) 4.36% ** 13.2(0.08) 3.07% ** 69.2(0.55)	7.49% ** 23.3(0.24)	0.48% ** 15.4(0.19)	0.81% ** 8.57(0.09)	7.28% ** 4.41(0.05)	5.86% **
	50-54 years	33.2(0.20)	13.0(0.08)	66.4(0.54)			23.4(0.23)		15.4(0.18)		8.00(0.09)	4.08(0.05)
	55-59 years	32.5(0.20)	12.9(0.08)	63.7(0.53)			23.3(0.23)		15.3(0.18)		7.57(0.09)	3.89(0.05)
	60-64 years	31.4(0.19)	12.5(0.08)	59.9(0.51)			22.8(0.22)		14.8(0.17)		6.96(0.09)	3.55(0.05)
	65-69 years	30.4(0.20)	12.2(0.08)	56.9(0.53)			22.3(0.23)		14.3(0.18)		6.59(0.09)	3.36(0.05)
	70-75 years	29.1(0.29)	11.8(0.12)	53.9(0.77)			21.8(0.33)		13.8(0.26)		5.99(0.13)	3.00(0.08)
	Gender
	women	33.1(0.18) 5.24% ** 13.1(0.07) 4.38% ** 64.2(0.49)	2.23% ** 23.0(0.21)	0.05% * 15.3(0.17)	0.80% ** 7.34(0.08)	0.03% * 3.78(0.05)	0.13% **
	men	30.2(0.18)	12.1(0.07)	59.1(0.49)			22.6(0.21)		14.3(0.16)		7.22(0.08)	3.65(0.05)
	Years of education

Table 3 :

 3 Effect Size using the Cohen's d: difference between the adjusted means divided (standardized) by the pooled standard deviation of the neuropsychological test scores

	Age		FCSRT Free recall	FCSRT Delayed free recall	DDST	Semantic Fluency	Phonemic Fluency	TMT-A	TMT
	50-54	45-49	-0.08	-0.11 **	-0.19 **	0.01	-0.01	-0.22 **	-0.
	55-59	50-54	-0.13 **	-0.08	-0.19 **	-0.02	-0.01	-0.18 **	-0.
	60-64	55-59	-0.21 **	-0.19 **	-0.27 **	-0.08	-0.12 **	-0.27 **	-0.
	65-69	60-64	-0.18 **	-0.13 **	-0.22 **	-0.09 *	-0.09 **	-0.18 **	-0.
	70-75	65-69	-0.24 **	-0.17 **	-0.22 **	-0.08	-0.12	-0.30 **	-0.
	Gender
	men	women	-0.54 **	-0.49 **	-0.35 **	-0.05 **	-0.21 **	-0.05 *	-0.
	Years of education
	16 years	17 years or more	-0.04	-0.03	-0.11 *	-0.07	-0.12 *	-0.08	-0.
	14 to 15 years	16 years	-0.17 **	-0.13 **	-0.06	-0.03	-0.08	0.03	-0
	12 to 13 years	14 to 15 years	-0.12 **	-0.11 **	-0.08	-0.23 **	-0.18 **	-0.06	-0.
	11 to 12 years	12 to 13 years	-0.26 **	-0.18 **	-0.42 **	-0.29 **	-0.44 **	-0.18 **	-0.
	5 to 11 years	11 to 12 years	0.03	0.01	0.01	0.01	0.03	-0.01	0
	less than 5 years 5 to 11 years	-0.33 **	-0.21 **	-0.67 **	-0.31 **	-0.49 **	-0.27 **	-0.
	Smoking
	Never	Current	0.02	-0.00	0.12 **	-0.10 *	-0.05	0.01	0
	Former	Current	0.01	-0.01	0.14 **	-0.02	0.01	0.09	0.
	Alcohol drinking
	Abstinent	Moderate	-0.04	-0.05	-0.05	-0.06	-0.12 **	-0.02	-
	Occasional	Moderate	-0.03	-0.03	0.01	-0.03	-0.08 **	-0.02	0
	Heavy	Moderate	0.01	-0.02	-0.02	0.03	0.03	-0.06	-0
	Physical Activity
	Very low	High	-0.04	-0.02	-0.02	-0.05	-0.08 **	-0.02	0
	Low	High	0.01	0.00	-0.04	-0.01	-0.05	-0.02	0
	Moderate	High	0.00	-0.01	-0.01	0.00	-0.04	-0.04	0

† Adjusted mean (±Standard Error of the Mean): Adjusted for all covariates shown in the table and for the inclusion center. *p<0.05 and **p<0.01 for the pairwise comparisons using Tukey's multiple comparison procedures to control for the family-wise error rate.

Acknowledgements: The authors thank the "Population-based Epidemiologic Cohorts Unit" UMS 011 INSERM-UVSQ that designed and manages the CONSTANCES Cohort Study.

They also thank the National Health Insurance Fund ("Caisse nationale d'assurance maladie des travailleurs salaries", CNAMTS) and its health screening centers ("Centres d'examens de santé") for collecting a large part of the data, as well as the National Retirement Fund (Caisse nationale d'assurance vieillesse), ClinSearch, Asqualab and Eurocell for the data quality control.


Marc Urvois
email: m.urvois@brgm.fr-rgf.brgm.fr

Thierry Baudin

Florence Cagnard

Philippe Calcagno

Nicolas Chauvin

Ulrich Clain

Santiago Gabillard

Sandrine Grataloup

B. ISSAUTIER Sylvain Grellet

Benoit Issautier

F Lacquement

B Le Bayon

F Lyonnais

A Marquant

P Nehlig

D Rambourg

C Ricordel-Prognon

J.-B Roquencourt

The Spatial Data Infrastructure for the Geological Reference of France

de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

From the geological map to the geological information infrastructure…

In continuation of the national programme of geological map of France at 1:50,000, the French Geological Survey (BRGM) engaged in the Geological Reference of France (Référentiel Géologique de la France, RGF) Also refer to a RGF dedicated presentation Theme T3.8 -31/08 10:30-12

>>

  :00) > New context and paradigm > Proof of concept: Vosges-Fossé Rhénan region > Principles and objectives of this new SDI at the French Geological Survey > Target system, architecture and data modelling > Data dissemination and Interoperability > Collect data (national inventories) > Store & Manage (national custodians) > Valorise (generate added value) > Ensure availability (in paper & digital form) > Contribute to the promotion of the sustainable use of non-renewable resources (attractiveness key factor in mineral sector development) > Contribute to geohazards mitigation > Support to geoscientific knowledge and skills > Support the informed decision-making Evolution of missions: data collection and map production => information capitalisation and dissemination Geological mapping: evolution of the paradigm > RGF = Scientific Programme + Information System => new "production line" > RGF mobilises a network of contributors from the Survey (BRGM), universities and private sector > Evolution from the publication of geological maps stored in a database to a dynamic SDI to generate end-user oriented products > Evolution from a 2D mapping paradigm to a 3D-4D multi-actor approach > Ensure the three-dimensional consistency of the geological data at regional for the French geologists > The national network of contributors to the RGF programme includes BRGM geologists, university researchers and students on 5-year regional projects > Supervision and validation by a Scientific Committee > Facilitated direct access for the registered contributors to the information system through a web extranet environment Ambitious innovative project: first stage (5 years) of a permanent infrastructure > Design and implementation jointly with the scientific research programme on Pyrénées > Timely with the mature level of a range of methods, processes, standards and obligations Core of the Geoscientific information system of the French Geological Survey (hydrogeology, mineral resources) > Provider of master data to other French SDIs (underground water, mineral resources, geothermal energy, …) > Provider to international infrastructures e.g. EGDI, EPOS and OneGeology: French contribution re. geological data and knowledge (observations and interpretations) > Built on international collaborative projects experience such as OneGeology-Europe, Minerals4EU, EuroGEOSS, etc. 30/08/2016 > 12

IGC35, Cape Town -Symposium T7.6

Data dissemination and interoperability

The SDI of the "Référentiel Géologique de la France" is designed and developed according to the state-of-the art regarding the Public Sector

An Information System for the RGF (2014 -…)

The RGF Information System must provide the best available geological information on the French territory, whatever the producer (French Geological Survey, universities, Earth science research institutes, …) through validation and traceability processes which define and guarantee the quality of data and knowledge that are capitalised and disseminated.