Jean-François Dartigues

University of Bordeaux, Burdeos, Aquitaine, France

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Publications (235)1244.62 Total impact

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    ABSTRACT: To establish normative data of retinal nerve fibre layer (RNFL) thickness in the elderly and to determine the factors influencing its thickness. Peripapillary RNFL thickness was measured with spectral domain OCT (SD-OCT) in 210 elderly participants from the Alienor population-based study who were aged 75 years or older. The measure was assessed in six segments (the superotemporal, temporal, inferotemporal, inferonasal, nasal and superonasal segments). RNFL data were analysed across age and sex strata in non-glaucoma participants. Mixed linear models were used to evaluate the associations of RNFL thickness with age, sex, ocular parameters and vascular risk factors. The mean global RNFL thickness was 91.4 μm (SD: 12.6), ranging from 55 to 122; the highest values were found in the inferotemporal and superotemporal segments. After adjustment for sex and ocular parameters, including axial length, increasing age was significantly associated with lower thickness globally (mean thinning per decade = 5.6 μm, p = 0.003), in the superotemporal (-12.7 μm per decade, p < 0.0001) and inferotemporal (-8.1 μm per decade, p = 0.022) segments. RNFL thickness tended to be higher in women than in men, but this trend was significant only in the inferotemporal segment (+6.6 μm for women, p = 0.012). The axial length was associated with RNFL thickness globally and in most segments. RNFL thickness did not differ according to cataract extraction. There were no associations between vascular factors and RNFL thickness. Retinal nerve fibre layer thickness decreased with age globally and in the supero- and inferotemporal segments, even after 75 years; it also tended to be higher in women, particularly in the inferotemporal segment. Normative data on RNFL thickness should consider these characteristics as well as ocular parameters, particularly axial length. © 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.
    Acta ophthalmologica 01/2015; · 2.44 Impact Factor
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    ABSTRACT: The identification of biological and pathophysiological processes implicated in different forms of dementia is itself dependent on reliable descriptions of cognitive performance and capacities. However, traditional instruments are often unable to detect subtle declines in cognitive functions due to natural variation at the time of testing. Mobile technologies permit the repeated assessment of cognitive functions and may thereby provide more reliable descriptions of early cognitive difficulties that are inaccessible to clinic or hospital-based instruments. This assessment strategy is also able to characterize in real-time the dynamic associations between cognitive performance and specific daily life behaviors or activities. In a cohort of elderly rural residents, 60 individuals were administered neuropsychological and neuroimaging exams as well as a one-week period of electronic ambulatory monitoring of behavior, semantic memory performance, and daily life experiences. Whereas imaging markers were unrelated to traditional neuropsychological test scores, they were significantly associated with mobile assessments of semantic memory performance. Moreover, certain daily life activities such as reading or completing crossword puzzles were associated with increases in semantic memory performance over the subsequent hours of the same day. The revolution in mobile technologies provides unprecedented opportunities to overcome the barriers of time and context that characterize traditional hospital and clinical-based assessments. The combination of both novel and traditional methods should provide the best opportunity for identifying the earliest risk factors and biomarkers for Alzheimer's disease and other forms of dementia.
    PLoS ONE 12/2014; 9(12):e112197. · 3.53 Impact Factor
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    ABSTRACT: The contribution of carotid atherosclerosis to incident dementia remains unclear. We examined the association between carotid plaques (CP) and common carotid intima media thickness (CCA-IMT) with incident dementia and its subtypes, and their added value for dementia risk prediction. At baseline, 6025 dementia-free subjects aged 65-86 years underwent bilateral carotid ultrasonography measures of CP and plaque-free CCA-IMT. Subjects were followed-up over 7 years for the detection of dementia. After a mean 5.4 years of follow-up, 421 subjects developed dementia including 272 Alzheimer's disease and 83 vascular/mixed dementia (VaD). Only CP were independently related to VaD (HR≥2 sites with plaques = 1.92; 95% confidence interval or CI = 1.13-3.22) and improved VaD risk prediction (continuous Net Reclassification Index = 30.1%; 95%CI = 8.4-51.7) beyond known dementia risk factors. Accounting for stroke or competing risk by death marginally modified the results. In older adults, CP are independent predictors of incident VaD and may improve VaD risk prediction. Copyright © 2014. Published by Elsevier Inc.
    Alzheimer's & dementia: the journal of the Alzheimer's Association 12/2014; · 14.48 Impact Factor
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    ABSTRACT: Purpose: While exposure to ultraviolet radiation is a recognized risk factor for cataract, its association is more controversial with age-related macular degeneration (AMD). We report the associations of lifetime exposure to ambient ultraviolet radiation (UVR) with cataract extraction and AMD. Methods: The Alienor Study is a population-based study of 963 residents of Bordeaux (France), aged 73 years or more. Lifetime exposure to ambient UVR was estimated from residential history and Eurosun satellite-based estimations of ground UVR. It was divided in 3 groups (lower quartile, intermediate quartiles, upper quartile), using the intermediate quartiles as the reference. Early and late AMD were classified from retinal colour photographs. Cataract extraction was defined as absence of the natural lens at slit lamp. Results: After multivariate adjustment, subjects in the upper quartile of lifetime ambient UVR exposure were at increased risk for cataract extraction (OR=1.53, 95 % confidence interval (CI): 1.04-2.26, p=0.03) and for early AMD (OR= 1.59, 95 % CI: 1.04-2.44, p=0.03), by comparison with subjects in the intermediate quartiles. Subjects in the lower quartile of UVR exposure were also at increased risk for early AMD (OR=1.69, 95 % CI: 1.06-2.69, p=0.03), by comparison with those with medium exposure. Associations of late AMD with UVR exposure was not statistically significant. Conclusions: This study further confirms the increased risk for cataract extraction in subjects exposed to high ambient UVR. Moreover, it suggests that risk for early AMD is increased in subjects exposed to high UVR, but also to low UVR, by comparison with medium exposures.
    Investigative Ophthalmology &amp Visual Science 10/2014; · 3.66 Impact Factor
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    ABSTRACT: Motivation Diseases that progress slowly are often studied by observing cohorts at different stages of disease for short periods of time. The Alzheimer's Disease Neuroimaging Initiative (ADNI) follows elders with various degrees of cognitive impairment, from normal to impaired. The study includes a rich panel of novel cognitive tests, biomarkers, and brain images collected every 6 months for as long as 6 years. The relative timing of the observations with respect to disease pathology is unknown. We propose a general semiparametric model and iterative estimation procedure to estimate simultaneously the pathological timing and long-term growth curves. The resulting estimates of long-term progression are fine-tuned using cognitive trajectories derived from the long-term “Personnes Agées Quid” study. Results We demonstrate with simulations that the method can recover long-term disease trends from short-term observations. The method also estimates temporal ordering of individuals with respect to disease pathology, providing subject-specific prognostic estimates of the time until onset of symptoms. When the method is applied to ADNI data, the estimated growth curves are in general agreement with prevailing theories of the Alzheimer's disease cascade. Other data sets with common outcome measures can be combined using the proposed algorithm. Availability Software to fit the model and reproduce results with the statistical software R is available as the grace package. ADNI data can be downloaded from the Laboratory of NeuroImaging.
    Alzheimer's & dementia: the journal of the Alzheimer's Association 10/2014; · 14.48 Impact Factor
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    Cécile Proust-Lima, Jean-François Dartigues, Hélène Jacqmin-Gadda
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    ABSTRACT: Joint models initially dedicated to a single longitudinal marker and a single time-to-event need to be extended to account for the rich longitudinal data of cohort studies. Multiple causes of clinical progression are indeed usually observed, and multiple longitudinal markers are collected when the true latent trait of interest is hard to capture (e.g. quality of life, functional dependency, cognitive level). These multivariate and longitudinal data also usually have nonstandard distributions (discrete, asymmetric, bounded,...). We propose a joint model based on a latent process and latent classes to analyze simultaneously such multiple longitudinal markers of different natures, and multiple causes of progression. A latent process model describes the latent trait of interest and links it to the observed longitudinal outcomes using flexible measurement models adapted to different types of data, and a latent class structure links the longitudinal and the cause-specific survival models. The joint model is estimated in the maximum likelihood framework. A score test is developed to evaluate the assumption of conditional independence of the longitudinal markers and each cause of progression given the latent classes. In addition, individual dynamic cumulative incidences of each cause of progression based on the repeated marker data are derived. The methodology is validated in a simulation study and applied on real data about cognitive aging coming from a large population-based study. The aim is to predict the risk of dementia by accounting for the competing death according to the profiles of semantic memory measured by two asymmetric psychometric tests.
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    ABSTRACT: Background: The Mini-Mental State Examination (MMSE) is widely used in population-based longitudinal studies to quantify cognitive change. However, its poor metrological properties, mainly ceiling/floor effects and varying sensitivity to change, have largely restricted its usefulness. We propose a normalizing transformation that corrects these properties, and makes possible the use of standard statistical methods to analyze change in MMSE scores. Methods: The normalizing transformation designed to correct at best the metrological properties of MMSE was estimated and validated on two population-based studies (n = 4,889, 20-year follow-up) by cross-validation. The transformation was also validated on two external studies with heterogeneous samples mixing normal and pathological aging, and samples including only demented subjects. Results: The normalizing transformation provided correct inference in contrast with models analyzing the change in crude MMSE that most often lead to biased estimates of risk factors and incorrect conclusions. Conclusions: Cognitive change can be easily and properly assessed with the normalized MMSE using standard statistical methods such as linear (mixed) models. © 2014 S. Karger AG, Basel.
    Neuroepidemiology 09/2014; 43(1):15-25. · 2.48 Impact Factor
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    ABSTRACT: Early detection of subjects at high risk of developing dementia is essential. By dealing with censoring and competing risk of death, we developed a score for predicting 10-year dementia risk by combining cognitive tests, and we assessed whether inclusion of cognitive change over the previous year increased its discrimination. Data came from the French prospective cohort study Personnes Agées QUID (PAQUID) and included 3,777 subjects aged 65 years or older (1988-1998). The combined prediction score was estimated by means of an illness-death model handling interval censoring and competing risk of death. Its predictive ability was measured using the receiver operating characteristic (ROC) curve, with 2 different definitions depending on the way subjects who died without a dementia diagnosis were considered. To account for right-censoring and interval censoring, we estimated the ROC curves by means of a weighting approach and a model-based imputation estimator. The combined score exhibited an area under the ROC curve (AUROC) of 0.81 for discriminating future demented subjects from subjects alive and nondemented 10 years later and an AUROC of 0.75 for discriminating future demented subjects from all other subjects (including deceased persons). Adjustment for cognitive change over the previous year did not improve prediction.
    American Journal of Epidemiology 09/2014; · 4.98 Impact Factor
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    ABSTRACT: ABSTRACT Background: To date, no studies have examined the relationship between cognitive disorders and personality disorders. Our aim was to investigate the association between dependent personality disorder (DPD) and cognitive disorders in Central Africa. Methods: Between 2011 and 2012, a cross-sectional multicenter population-based study was carried out in rural and urban areas of the Central African Republic (CAR) and the Republic of Congo (ROC). Participants aged ≥65 years were interviewed using the Community Screening Interview for Dementia (CSI-D). Elderly people who performed poorly (CSI-D cognitive tests score or COGSCORE ≤ 24.5/30) were clinically assessed by neurologists and underwent further psychometric testing. The Diagnostic and Statistical Manual of Mental Disorders, 4th Edition and Petersen criteria were required for the diagnosis of dementia and mild cognitive impairment (MCI) respectively. DPD was assessed using the Personality Diagnostic Questionnaire-4+. Socio-demographic, vascular, and psychological factors were also documented. Multivariate multinomial logistic regression models were used to estimate the associations. Results: Of the 2,002 participants screened, 860 and 912 had data for cognitive status and DPD in CAR and ROC respectively. In fully adjusted models, DPD was significantly associated with MCI in ROC (Odds Ratio (OR) = 2.2, 95% CI: 1.0-4.7) and CAR (OR = 2.1, 95% CI: 1.1-4.0) and with dementia only in ROC (OR = 4.8, 95% CI: 2.0-11.7). Conclusions: DPD was associated with cognitive disorders among elderly people in Central Africa. This association should be confirmed in other contexts. This study paves the way for research on the association between personality and cognitive impairment in Africa.
    International Psychogeriatrics 09/2014; · 1.89 Impact Factor
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    ABSTRACT: The DMS 48 is a visual recognition memory test designed to detect memory changes in early Alzheimer's disease (AD). The aim of this study was to produce normative scores for this test and to assess its psychometric properties in the detection of AD by comparison with a widely used test of verbal episodic memory: the story recall task of the Wechsler memory scale. Methods. Data were collected in a sample of 1002 agricultural retirees, aged 65 years and over, included in the AMI study, a population-based cohort conducted in Southwestern France. The sample used to establish normative data included 750 non-demented elderly while the sample used to study the properties of the test to detect AD included 751 participants whose 34 with AD. To assess AD detection accuracy, DMS 48 was compared to the Wechsler story recall task. Results. Age, sex, and education were significantly associated with DMS 48 performances. Therefore, normative scores were calculated according to sex, age, and educational level, and described by percentiles. Regarding the test properties for AD detection, DMS 48 presented a good balance between sensitivity (Se) and specificity (Sp) both for immediate (Se = 70.6%; Sp = 79.6%) and delayed recall (Se = 79.4%; Sp = 72.9%). It also showed high negative predictive values, around 98.5% for both recalls. Detection values were roughly similar to that of Wechsler story recall task. Conclusion: The DMS 48 seems to be as reliable as the Wechsler story recall task with similar detection properties. The DMS 48 is a test easy to administer in clinical situations and could be a helpful tool for AD screening.
    Geriatrie et psychologie neuropsychiatrie du vieillissement 09/2014; 12(3):321-330. · 0.40 Impact Factor
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    ABSTRACT: We investigated the use of Alzheimer's disease (AD) biomarkers in European Alzheimer's Disease Consortium centers and assessed their perceived usefulness for the etiologic diagnosis of mild cognitive impairment (MCI). We surveyed availability, frequency of use, and confidence in diagnostic usefulness of markers of brain amyloidosis (amyloid positron emission tomography [PET], cerebrospinal fluid [CSF] Aβ42) and neurodegeneration (medial temporal atrophy [MTA] on MR, fluorodeoxyglucose positron emission tomography [FDG-PET], CSF tau). The most frequently used biomarker is visually rated MTA (75% of the 37 responders reported using it “always/frequently”) followed by CSF markers (22%), FDG-PET (16%), and amyloid-PET (3%). Only 45% of responders perceive MTA as contributing to diagnostic confidence, where the contribution was rated as “moderate”. Seventy-nine percent of responders felt “very/extremely” comfortable delivering a diagnosis of MCI due to AD when both amyloid and neuronal injury biomarkers were abnormal (P < .02 versus any individual biomarker). Responders largely agreed that a combination of amyloidosis and neuronal injury biomarkers was a strongly indicative AD signature.
    Alzheimer's and Dementia 08/2014; · 17.47 Impact Factor
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    ABSTRACT: A large proportion of dementia cases are still undiagnosed. Although early dementia care has been hypothesized to benefit both patients and families, evidence-based benefits are lacking. Thus, investigating the benefits for newly demented persons according to their recourse to care in the "real life" appears critical.
    Alzheimer's & dementia: the journal of the Alzheimer's Association 08/2014; · 14.48 Impact Factor
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    ABSTRACT: Background: The worldwide population is ageing and the proportion of elderly aged 60 and over is expected to dramatically rise in Low and Middle Income Countries (LMIC). The epidemic of dementia will not spare those countries, where the largest increases in numbers of people affected are estimated. Besides, dementia is still understudied in sub-Saharan Africa (SSA) compared to other regions. This paper describes the protocol for the ‘Epidemiology of Dementia in Central Africa'population-based study, which aims at estimating the prevalence of dementia in two countries of Central Africa and investigating possible risk factors. Methods/Design: A multicenter population-based study was carried out in Central African Republic and Republic of Congo between 2011 and 2012 including both urban and rural sites in each country. Around 2000 participants aged ≥ 65 years old were interviewed in total using the Community Screening Interview for Dementia (CSI-D), the GMS-AGECAT and the CERAD’s 10-word list. Elderly with low performance to the cognitive part of the CSI-D (COGSCORE ≤ 24.5) were then clinically assessed by neurologists and underwent further psychometrical tests. DSM-IV and NINCDS-ADRDA criteria were required for dementia and Alzheimer’s disease (AD) diagnoses respectively. The algorithmic 10/66 dementia diagnosis was also determined. Petersen’s criteria were required for the diagnosis of Mild Cognitive Impairment. Sociodemographic, and environmental factors including vascular, nutritional, biological, psychosocial and lifestyle factors were collected in each setting in order to investigate factors associated with dementia. Blood sampling was realized to investigate genetic variations that could modify the risk of dementia. Discussion: For now, no large epidemiological study has been undertaken to compare the prevalence of dementia in both rural and urban areas within SSA countries. This programme will provide further evidence regarding the prevalence of dementia in SSA, and also the possible rural/urban disparities existing with associated factors. Furthermore, the genetics of AD in those populations will be addressed.
    SpringerPlus 07/2014;
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    ABSTRACT: Objective The objective of this study is to compare cognitive decline of elderly people after entering an institution with that of elders living in the community with similar clinical conditions. Design The Personnes Agées QUID (PAQUID) cohort is a prospective population-based study which included, at baseline, 3777 community-dwelling people aged 65 years and older. Participants were followed-up for 22 years. Among those who were nondemented and living at home at baseline, 2 groups were compared: participants who entered a nursing home during study follow-up (n = 558) and those who remained living at home (n = 3117). Cognitive decline was assessed with Mini-Mental State Examination (MMSE), Benton visual retention test, and verbal fluency Isaacs Set Test. Results After controlling for numerous potential confounders, including baseline MMSE and instrumental activities of daily living scores, incident dementia, depressive symptoms, and chronic diseases, nursing home placement was significantly associated with a lower score on MMSE between the last visit before and after institutionalization (difference of 2.8 points, P < .0001) and greater further cognitive decline after institutionalization (difference of 0.7 point per year, P < .0001). Similar results were found for the Benton memory test. In a second series of analysis in which the persons who became demented over the study follow-up were excluded, the results remained unchanged. Conclusions The present study suggests that institutionalized elderly people present a greater cognitive decline than persons remaining in the community. The reasons of that decline remain unclear and may be related to physical and psychological effects of institutionalization in elderly people.
    Journal of the American Medical Directors Association 07/2014; · 5.30 Impact Factor
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    ABSTRACT: Semicompeting risks and interval censoring are frequent in medical studies, for instance when a disease may be diagnosed only at times of visit and disease onset is in competition with death. To evaluate the ability of markers to predict disease onset in this context, estimators of discrimination measures must account for these two issues. In recent years, methods for estimating the time-dependent receiver operating characteristic curve and the associated area under the ROC curve have been extended to account for right censored data and competing risks. In this paper, we show how an approximation allows to use the inverse probability of censoring weighting estimator for semicompeting events with interval censored data. Then, using an illness-death model, we propose two model-based estimators allowing to rigorously handle these issues. The first estimator is fully model based whereas the second one only uses the model to impute missing observations due to censoring. A simulation study shows that the bias for inverse probability of censoring weighting remains modest and may be less than the one of the two parametric estimators when the model is misspecified. We finally recommend the nonparametric inverse probability of censoring weighting estimator as main analysis and the imputation estimator based on the illness-death model as sensitivity analysis.
    Statistical Methods in Medical Research 05/2014; · 2.96 Impact Factor
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    ABSTRACT: Cognitive lifestyle measures such as education, occupation, and social engagement are commonly associated with late-life cognitive ability although their associations with cognitive decline tend to be mixed. However, longitudinal analyses of cognition rarely account for death and dropout, measurement error of the cognitive phenotype, and differing trajectories for different population sub-groups. This paper applies a joint latent class mixed model (and a multi-state model in a sensitivity analysis) that accounts for these issues to a large (n = 3,653), population-based cohort, Paquid, to model the relationship between cognitive lifestyle and cognitive decline. Cognition was assessed over a 20-year period using the Mini-Mental State Examination. Three cognitive lifestyle variables were assessed: education, mid-life occupation, and late-life social engagement. The analysis identified four latent sub-populations with class-specific longitudinal cognitive decline and mortality risk. Irrespective of the cognitive trajectory, increased social engagement was associated with a decreased mortality risk. High education was associated with the most favourable cognitive trajectory, and after adjusting for cognitive decline, with an increased mortality risk. Mid-life occupational complexity was also associated with more favourable trajectories but not with mortality risk. To realistically examine the link between cognitive lifestyle and cognitive decline, complex statistical models are required. This paper applies and compares in a sensitivity analysis two such models, and shows education to be linked to a compression of cognitive morbidity irrespective of cognitive trajectory. Furthermore, a potentially modifiable variable, late-life social engagement is associated with a decreased mortality risk in all of the population sub-groups.
    European Journal of Epidemiology 02/2014; · 5.15 Impact Factor
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    ABSTRACT: A better knowledge of long-term trajectories of cognitive decline is a central feature of the study of the process leading to Alzheimer's dementia. Several factors may mitigate such decline, among which is education, a major risk factor for Alzheimer's disease. The aim of our work was to compare the pattern and duration of clinical trajectories before Alzheimer's dementia in individuals with low and high education within the PAQUID cohort involving 20 years of follow-up. The sample comprises 442 participants with incident Alzheimer's disease (27.2% were male)-171 with low education (mean age = 86.2 years; standard deviation = 5.3 years) and 271 with higher education (mean age = 86.5; standard deviation = 5.4)-and 442 control subjects matched according to age, sex and education. At each visit and up to the 20-year follow-up visit, several cognitive and clinical measures were collected and incident cases of Alzheimer's disease clinically diagnosed. The evolution of clinical measures in pre-demented subjects and matched controls was analysed with a semi-parametric extension of the mixed effects linear model. The results show that the first signs of cognitive decline occurred 15 to 16 years before achieving dementia threshold in higher-educated subjects whereas signs occurred at 7 years before dementia in low-educated subjects. There seemed to be two successive periods of decline in higher-educated subjects. Decline started ∼15 to 16 years before dementia with subtle impairment restricted to some cognitive tests and with no impact during the first 7 to 8 years on global cognition, cognitive complaints, or activities of daily living scales. Then, ∼7 years before dementia, global cognitive abilities begin to deteriorate, along with difficulties dealing with complex activities of daily living, the increase in self-perceived difficulties and depressive symptoms. By contrast, lower-educated subjects presented a single period of decline lasting ∼7 years, characterized by decline concomitantly affecting specific and more global cognitive function along with alteration in functional abilities. This study demonstrates how early cognitive symptoms may emerge preceding Alzheimer's dementia particularly in higher-educated individuals, for whom decline occurred up to 16 years before dementia. It also demonstrates the protective role of education in the clinical trajectory preceding Alzheimer's dementia. We suggest that the initial decline in cognition occurs at the onset of comparable Alzheimer's disease pathology in both groups, and is associated with immediate decline to dementia in the lower education group. In contrast, higher education protects against further cognitive decline for ∼7 years until pathology becomes more severe.
    Brain 02/2014; · 10.23 Impact Factor
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    ABSTRACT: We aimed to investigate the impact of endogenous estradiol (E2) on dementia and to evaluate the contribution of vascular risk factors and inflammatory and blood coagulation markers to this association. Using data from a French population-based prospective study (the Three-City Study) including 5,644 postmenopausal women aged 65 years or older, we investigated the association of endogenous total-E2 and bioavailable-E2 and total-testosterone with the 4-year incidence of all-cause dementia. We further focused on the role of dementia and cardiovascular risk factors as well as inflammation (C-reactive protein, fibrinogen) and hypercoagulability (fibrin d-dimers, thrombin generation) in these associations. We used a case-cohort design consisting of a random subcohort of 562 women not using hormone therapy and 132 incident dementia cases. Adjusted Cox proportional hazards models showed a J-shaped relationship between total-E2 and risk of dementia (p = 0.001). Total-E2 values in the lower and upper quartiles were associated with an increased dementia risk (adjusted hazard ratio [HR] [95% confidence interval] = 2.2 [1.1-4.5] and HR = 2.4 [1.2-5.2], respectively). Importantly, the risk associated with higher E2 levels was dramatically increased in women with diabetes compared with nondiabetic women (adjusted HR associated with the upper E2 quartile = 14.2 [1.60-123] and HR = 3.4 [0.1-147], respectively, p interaction <0.05). Similar results were found for bioavailable-E2. Adjustment for inflammatory and blood coagulation markers did not modify our results. No significant association was found for total-testosterone. High E2 level is an independent predictor of incident dementia, particularly in postmenopausal women with diabetes.
    Neurology 01/2014; · 8.30 Impact Factor
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    ABSTRACT: Structural alterations of a large network characterize Alzheimer's disease (AD), but the time course of these changes remains unclear. The dynamic of these alterations was examined in the AD preclinical phase using data from the 10-year follow-up of a population-based cohort (Bordeaux-3City). Participants received neuropsychological assessments every 2 years and two identical magnetic resonance imaging (MRI) exams at baseline and 4 years later. Twenty-five incident AD cases were compared with 319 subjects who remained free of dementia. Subjects were free of dementia at baseline and at follow-up MRI. Incident AD occurred after these time points. At baseline, incident AD already presented smaller volumes only in the left amygdalo-hippocampal complex. Moreover, a higher annual rate of atrophy of the temporoparietal cortices was observed in future AD subjects during the following 4 years. Incident AD cases present mediotemporal lesions up to 5 years before diagnosis. This neurodegenerative process seems to progressively reach the temporoparietal cortices in the AD preclinical phase.
    Alzheimer's & dementia: the journal of the Alzheimer's Association 01/2014; · 14.48 Impact Factor

Publication Stats

5k Citations
1,244.62 Total Impact Points


  • 2004–2014
    • University of Bordeaux
      Burdeos, Aquitaine, France
  • 2000–2014
    • Université Victor Segalen Bordeaux 2
      • Institut de Santé Publique d'Epidémiologie et de Développement (ISPED)
      Burdeos, Aquitaine, France
  • 1994–2014
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 2013
    • The Royal Children's Hospital
      Melbourne, Victoria, Australia
    • Université Paris-Sud 11
      Orsay, Île-de-France, France
  • 2007–2013
    • Pierre and Marie Curie University - Paris 6
      Lutetia Parisorum, Île-de-France, France
  • 2005–2013
    • French Institute of Health and Medical Research
      • Centre de Recherche en Épidémiologie et Santé des Populations CESP U1018
      Lutetia Parisorum, Île-de-France, France
  • 2009–2012
    • Université de Montpellier 1
      • Faculté de Pharmacie
      Montpelhièr, Languedoc-Roussillon, France
    • University of Limoges
      • Institut d'Epidémiologie Neurologique et de Neurologie Tropicale (IENT)
      Limages, Limousin, France
  • 2008–2012
    • Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
      Tlalpam, The Federal District, Mexico
    • Centre Hospitalier Universitaire de Bordeaux
      Burdeos, Aquitaine, France
    • Groupe hospitalier "Broca - La Rochefoucauld - La Collégiale" – Hôpitaux universitaires Paris Centre
      Lutetia Parisorum, Île-de-France, France
  • 2011
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
    • Laval University
      Québec, Quebec, Canada
  • 2010–2011
    • Institut Pasteur de Lille
      Lille, Nord-Pas-de-Calais, France
  • 2002
    • Université de Montréal
      • Center for Mathematical Research
      Montréal, Quebec, Canada