Jean-François Dartigues

French Institute of Health and Medical Research, Lutetia Parisorum, Île-de-France, France

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Publications (296)1495.01 Total impact

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    ABSTRACT: Microstructural changes of White Matter (WM) associated with aging have been widely described through Diffusion Tensor Imaging (DTI) parameters. In parallel, White Matter Hyperintensities (WMH) as observed on a T2-MRI are extremely common in older individuals. However, few studies have investigated both phenomena conjointly. The present study investigates aging effects on DTI parameters in absence and in presence of WMH. Diffusion maps were constructed based on 21 directions DTI scans of young adults (n=19, mean age=33 SD=7.4) and two age-matched groups of older adults, one presenting low-level-WMH (n=20, mean age=78, SD= 3.2) and one presenting high-level-WMH (n=20, mean age=79, SD= 5.4). Older subjects with low-level-WMH presented modifications of DTI parameters in comparison to younger subjects, fitting with the DTI pattern classically described in aging, i.e. Fractional Anisotropy (FA) decrease/Radial Diffusivity (RD) increase. Furthermore, older subjects with high-level-WMH showed higher DTI modifications in Normal Appearing White Matter (NAWM) in comparison to those with low-level-WMH. Finally, in older subjects with high-level-WMH, FA or RD values of NAWM were associated with to WMH burden. Therefore, our findings suggest that DTI modifications and the presence of WMH would be two inter-dependent processes but occurring within different temporal windows. DTI changes would reflect the early phase of white matter changes and WMH would appear as a consequence of those changes.
    Full-text · Article · Feb 2016 · Frontiers in Aging Neuroscience

  • No preview · Article · Feb 2016
  • Arlette Edjolo · Cécile Proust-Lima · Fleur Delva · Jean-François Dartigues · Karine Pérès
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    ABSTRACT: We aimed to describe the hierarchical structure of Instrumental Activities of Daily Living (IADL) and basic Activities of Daily Living (ADL) and trajectories of dependency before death in an elderly population using item response theory methodology. Data were obtained from a population-based French cohort study, the Personnes Agées QUID (PAQUID) Study, of persons aged ≥65 years at baseline in 1988 who were recruited from 75 randomly selected areas in Gironde and Dordogne. We evaluated IADL and ADL data collected at home every 2–3 years over a 24-year period (1988–2012) for 3,238 deceased participants (43.9% men). We used a longitudinal item response theory model to investigate the item sequence of 11 IADL and ADL combined into a single scale and functional trajectories adjusted for education, sex, and age at death. The findings confirmed the earliest losses in IADL (shopping, transporting, finances) at the partial limitation level, and then an overlapping of concomitant IADL and ADL, with bathing and dressing being the earliest ADL losses, and finally total losses for toileting, continence, eating, and transferring. Functional trajectories were sex-specific, with a benefit of high education that persisted until death in men but was only transient in women. An in-depth understanding of this sequence provides an early warning of functional decline for better adaptation of medical and social care in the elderly.
    No preview · Article · Jan 2016 · American Journal of Epidemiology
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    ABSTRACT: Background: Sophisticated and expensive biomarkers are proposed for the diagnostic of Alzheimer's disease (AD). The amyloid process seems to be early in AD, and brain amyloid load affects the frontal lobe. Objective: To determine if certain simple clinical signs, especially frontal-related signs, could help reach an earlier and better diagnosis. Methods: In the frame of the 3-City cohort, we conducted a nested case-control study comparing incident cases of AD to controls matched for age, gender, and education. The standardized neurological exam included extrapyramidal signs (akinesia, rigidity, rest tremor), pyramidal symptoms (spastic rigidity, Babinski reflex), primitive reflexes (snout, palmomental reflex grasping), and tremor (essential, intentional, head) at the time of diagnosis and two years before. Results: We compared 106 incident AD subjects (mean age at diagnosis 82.2 (SD = 5.9); median MMSE at diagnosis = 23) to 208 matched controls. In patients younger than 80, palmomental reflexes were more frequent in AD than controls, two years before diagnosis (25.0 versus 7.0% , p = 0.03) and at time of diagnosis (30.3 versus 12.3% , p = 0.02). No difference was observed for other signs two years before diagnosis or for patients older than 80. Conclusion: Before diagnosis, the clinical examination of AD patients is not strictly normal; the primitive reflexes appear to be pathological. It might be in connection with the frontal amyloid load at an early stage of the disease. Clinical examination can reveal simple and interesting signs that deserve consideration as well as the other more invasive and expensive biomarkers.
    Preview · Article · Dec 2015 · Journal of Alzheimer's disease: JAD
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    Kamel Gana · Yaël Saada · Guillaume Broc · Bruno Quintard · Hélène Amieva · Jean-François Dartigues
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    ABSTRACT: Objective: Reciprocal relationships between positive affect (PA) and health are now subject of a heuristic debate in psychology and behavioral medicine. Two radically opposed approaches address the link between subjective well being (SWB) and physical health: top-down (i.e., psychosomatic hypothesis) and bottom-up (i.e., disability/ability hypothesis) approaches. The aim of the present study was to test these two approaches by investigating thirteen-year longitudinal relationships between PA, as an affective dimension of SWB, and functional health in older people. Methods: The study included 3754 participants aged 62-101 years assessed 6 times over a thirteen-year period. PA was measured by the mean of the positive affect subscale of the CES-D scale. Functional health was assessed by four composite items: a single-item self-rating of hearing impairment, a single-item self-rating of vision impairment, the number of medically prescribed drugs, and a single-item self-rating of dyspnoea. We used cross-lagged modeling with latent variables, which is appropriate for testing specific theories. Mean arterial pressure, diabetes mellitus and hypercholesterolemia status, sequelae of stroke, gender, level of education, and age at baseline were use as control variables in the models. Results: Results indicated that good health significantly predicted subsequent levels of PA (average β = -0.58, p < 0.001), but PA did not predict subsequent levels of good health (β = 0.01, ns). Conclusion: This finding, obtained from a sample of older people, is in keeping with the bottom-up approach, and supports the popular adage "As long as you've got your health". Limitations of this finding are reviewed and discussed. Models including longitudinal mediators, such as biomarkers and life style patterns, are needed to clarify the nature of the link between these constructs.
    Full-text · Article · Nov 2015 · Social Science [?] Medicine
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    ABSTRACT: Background: Although non-drug interventions are widely used in patients with Alzheimer's disease, few large scale randomized trials involving a long-term intervention and several cognitive-oriented approaches have been carried out. ETNA3 trial compares the effect of cognitive training, reminiscence therapy, and an individualized cognitive rehabilitation program in Alzheimer's disease to usual care. Methods: This is a multicenter (40 French clinical sites) randomized, parallel-group trial, with a two-year follow-up comparing groups receiving standardized programs of cognitive training (group sessions), reminiscence therapy (group sessions), individualized cognitive rehabilitation program (individual sessions), and usual care (reference group). Six hundred fifty-three outpatients with Alzheimer's disease were recruited. The primary efficacy outcome was the rate of survival without moderately severe to severe dementia at two years. Secondary outcomes were cognitive impairment, functional disability, behavioral disturbance, apathy, quality of life, depression, caregiver's burden, and resource utilization. Results: No impact on the primary efficacy measure was evidenced. For the two group interventions (i.e. cognitive training and reminiscence), none of the secondary outcomes differed from usual care. The larger effect was seen with individualized cognitive rehabilitation in which significantly lower functional disability and a six-month delay in institutionalization at two years were evidenced. Conclusions: These findings challenge current management practices of Alzheimer's patients. While cognitive-oriented group therapies have gained popularity, this trial does not show improvement for the patients. The individualized cognitive rehabilitation intervention provided clinically significant results. Individual interventions should be considered to delay institutionalization in Alzheimer's disease.
    Full-text · Article · Nov 2015 · International Psychogeriatrics
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    ABSTRACT: Background: Benzodiazepine use has been associated with increased risk of dementia. However, it remains unclear whether the risk relates to short or long half-life benzodiazepines and whether it extends to other psychotropic drugs. Methods: Prospective cohort study among 8240 individuals ≥65, interviewed on medication use. Incident dementia confirmed by an end point committee after a multistep procedure. Results: During a mean of 8 years of follow-up, 830 incident dementia cases were observed. Users of benzodiazepines at baseline had a 10% increased risk of dementia (adjusted hazard ratio [HR], 1.10; 95% confidence interval, 0.90-1.34). However, long half-life (>20 hours) benzodiazepine users had a marked increased risk of dementia (HR = 1.62; 1.11-2.37) compared with short half-life users (HR = 1.05; 0.85-1.30). Users of psychotropics had an increased risk of dementia (HR = 1.47; 1.16-1.86). Conclusions: Results of this large, prospective study show increased risk of dementia for long half-life benzodiazepine and psychotropic use.
    No preview · Article · Nov 2015 · Alzheimer's & dementia: the journal of the Alzheimer's Association
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    ABSTRACT: Background: Identifying modifiable lifestyle correlates of cognitive decline and risk of dementia is complex, particularly as few population-based longitudinal studies jointly model these interlinked processes. Recent methodological developments allow us to examine statistically defined sub-populations with separate cognitive trajectories and dementia risks. Methods: Engagement in social, physical, or intellectual pursuits, social network size, self-perception of feeling well understood, and degree of satisfaction with social relationships were assessed in 2854 participants from the Paquid cohort (mean baseline age 77 years) and related to incident dementia and cognitive change over 20-years of follow-up. Multivariate repeated cognitive information was exploited by defining the global cognitive functioning as the latent common factor underlying the tests. In addition, three latent homogeneous sub-populations of cognitive change and dementia were identified and contrasted according to social environment variables. Results: In the whole population, we found associations between increased engagement in social, physical, or intellectual pursuits and increased cognitive ability (but not decline) and decreased risk of incident dementia, and between feeling understood and slower cognitive decline. There was evidence for three sub-populations of cognitive aging: fast, medium, and no cognitive decline. The social-environment measures at baseline did not help explain the heterogeneity of cognitive decline and incident dementia diagnosis between these sub-populations. Conclusions: We observed a complex series of relationships between social-environment variables and cognitive decline and dementia. In the whole population, factors such as increased engagement in social, physical, or intellectual pursuits were related to a decreased risk of dementia. However, in a sub-population analysis, the social-environment variables were not linked to the heterogeneous patterns of cognitive decline and dementia risk that defined the sub-groups.
    Full-text · Article · Oct 2015 · BMC Public Health
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    ABSTRACT: Objective: To determine whether and how age at retirement influences the risk of dementia. The association between the age at retirement, the number of working years and the risk of dementia was evaluated over 12 years of follow-up. Design: A prospective population-based study. Setting: Three-City cohort, a French population-based study of community-dwelling individuals aged 65 to 95. Participants: The sample consisted of 1,658 non-demented participants at baseline. Measurements: All participants were evaluated at home at the initial visit and at two years interval for a period of 12 years. An active research of dementia was conducted at each follow-up; all suspected cases were analysed by an independent committee of neurologists. Information regarding retirement age and number of working years was collected at baseline using a structured questionnaire. Results: The multivariate Cox model, including both the age at retirement and the number of working years and adjusted for potential confounders, revealed that the risk of dementia was independently associated with the age at retirement (p=0.022) but not with the number of working years (p=0.296). Conclusion: Although our results are in accordance with previous studies (i.e., older age at retirement is associated with decreased risk of dementia), it provides additional information regarding the possible explanation for such results. Given that a longer working life did not reduce the risk of dementia, the age at retirement cannot be considered as a new factor of cognitive reserve but rather seems to be a psycho-social vulnerability factor. Further evidence is necessary to identify work and retirement related factors that influence the association between the age at retirement and the risk of dementia.
    Full-text · Article · Oct 2015 · The Journal of Nutrition Health and Aging
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    ABSTRACT: Finding very early biomarkers of Alzheimer's Disease (AD) to aid in individual prognosis is of major interest to accelerate the development of new therapies. Among the potential biomarkers, neurodegeneration measurements from MRI are considered as good candidates but have so far not been effective at the early stages of the pathology. Our objective is to investigate the efficiency of a new MR-based hippocampal grading score to detect incident dementia in cognitively intact patients. This new score is based on a pattern recognition strategy, providing a grading measure that reflects the similarity of the anatomical patterns of the subject under study with dataset composed of healthy subjects and patients with AD. Hippocampal grading was evaluated on subjects from the Three-City cohort, with a followup period of 12 years. Experiments demonstrate that hippocampal grading yields prediction accuracy up to 72.5% (P < 0.0001) 7 years before conversion to AD, better than both hippocampal volume (58.1%, P = 0.04) and MMSE score (56.9%, P = 0.08). The area under the ROC curve (AUC) supports the efficiency of imaging biomarkers with a gain of 8.4 percentage points for hippocampal grade (73.0%) over hippocampal volume (64.6%). Adaptation of the proposed framework to clinical score estimation is also presented. Compared with previous studies investigating new biomarkers for AD prediction over much shorter periods, the very long followup of the Three-City cohort demonstrates the important clinical potential of the proposed imaging biomarker. The high accuracy obtained with this new imaging biomarker paves the way for computer-based prognostic aides to help the clinician identify cognitively intact subjects that are at high risk to develop AD. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc.
    Full-text · Article · Oct 2015 · Human Brain Mapping
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    Full-text · Dataset · Sep 2015
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    ABSTRACT: There is an obvious lack of validated norms for elderly persons aged 85 and older for the large majority of the neuropsychological tests used in clinical practice. Yet this range of “oldest-old” individuals drastically increases worldwide and is the more likely to develop dementia. Providing clinicians validated and updated norms to accurately evaluate cognitive functioning in this population is an important issue in geriatrics. This study provides normative scores for 7 neuropsychological tests commonly used in clinical practice. Data were collected in a sample of 283 subjects aged 85 and older, included in the PAQUID study, a population-based cohort conducted in France. Normative scores were calculated according to 2 age ranges and 2 educational levels, and are presented in percentiles. The norms provided in the present study involve 7 tests that are widely used in the neuropsychological assessment of geriatrics populations and should be of help for clinicians.
    No preview · Article · Sep 2015 · Archives of Clinical Neuropsychology
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    ABSTRACT: Although intake of fruits and vegetables has been associated with a decreased risk of dementia, studies focusing on nutrients underlying this association are lacking. Our objective was to analyze the relation between plasma carotenoids and the risk of dementia and Alzheimer's disease (AD) in French elderly community dwellers. The study population consisted of 1,092 nondemented older participants, from the Three-City-Bordeaux cohort followed for up to 10 years (range: 1.8-10.8 years, median: 9.5 years). Dementia and AD were diagnosed by a committee of neurologists. The concentration of plasma carotenoids (beta-carotene, alpha-carotene, lycopene, lutein, zeaxanthin, and beta-cryptoxanthin) was determined at baseline. Longitudinal analyses of the association between each plasma carotenoid, either crude or expressed as a ratio to plasma lipids (total cholesterol + triglycerides), and the risk of dementia or AD were performed by multivariate Cox models. During follow-up, 199 dementia cases, including 132 AD, occurred. After adjustment for sociodemographic data, diet quality, and clinical variables, including baseline cognitive performances, only higher lutein concentration, considered as a function of plasma lipids, was consistently significantly associated with a decreased risk of all-cause dementia and AD (hazard ratio = 0.808, 95% confidence interval = 0.671-0.973, p = .024 and hazard ratio = 0.759, 95% confidence interval = 0.600-0.960, p = .021, respectively for +1 SD). This large cohort of older participants suggests that maintaining higher concentrations of lutein in respect to plasma lipids may moderately decrease the risk of dementia and AD. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
    No preview · Article · Aug 2015 · The Journals of Gerontology Series A Biological Sciences and Medical Sciences

  • No preview · Conference Paper · Jul 2015
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    ABSTRACT: The Mediterranean diet (MeDi) has been related to a lower risk of Alzheimer's disease; yet, the underlying mechanisms are unknown. We hypothesized that protection against neurodegeneration would translate into higher gray matter volumes, whereas a specific association with preserved white matter microstructure would suggest alternative mechanisms (e.g., vascular pathways). We included 146 participants from the Bordeaux Three-City study nondemented when they completed a dietary questionnaire and who underwent a 3-T magnetic resonance imaging at an average of 9 years later, including diffusion tensor imaging. In multivariate voxel-by-voxel analyses, adherence to the MeDi was significantly associated with preserved white matter microstructure in extensive areas, a gain in structural connectivity that was related to strong cognitive benefits. In contrast, we found no relation with gray matter volumes. The MeDi appears to benefit brain health through preservation of structural connectivity. Potential mediation by a favorable impact on brain vasculature deserves further research. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
    Full-text · Article · Jul 2015 · Alzheimer's & dementia: the journal of the Alzheimer's Association
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    ABSTRACT: The present research sought to characterize the intrinsic functional networks associated with a 10-year episodic memory decline in elderly using data from a longitudinal population-based cohort (Bordeaux-3City). Complementary measures of whole-brain resting-state functional magnetic resonance imaging investigations were combined to compare functional architecture of brain networks both at connectional and topological levels in 22 decliners to 22 nondecliners; episodic memory decline being assessed through a multiple time point Free and Cued Selective Reminding Test. The decliners presented differences in functional architecture centered on the posterior cingulate cortex, characterized by a significant decrease of connectivity intensity, a significant increased centrality. In accordance, a decrease of the functional connectivity inside the default mode network was observed in the decliners. Our results highlight the central role of the posterior cingulate cortex in a slow but reliable memory decline in elderly. Because functional alterations of this region are currently described in Alzheimer's disease, this functional signature could constitute a risk for Alzheimer's disease. Copyright © 2015 Elsevier Inc. All rights reserved.
    No preview · Article · Jul 2015 · Neurobiology of aging
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    ABSTRACT: We investigated the relationship of diabetes and prediabetes with cognitive performances, assessed through raw test and z scores and according to neurocognitive impairment (NCI) classification in a cohort of individuals infected with HIV. The ANRS CO3 Aquitaine cohort is a prospective hospital-based cohort of HIV-1-infected patients under routine clinical management in 6 public hospitals in southwestern France. Between 2007 and 2009, an ancillary study consisted of a neuropsychological battery of 10 tests at baseline and 2-year follow-up. The severity of NCI (normal, asymptomatic, mild, HIV dementia) was assessed according to international guidelines. At baseline (400 patients, 33 with prediabetes, 39 with diabetes), in cross-sectional multivariable analyses, patients with diabetes performed significantly worse on 9 neuropsychological tests that assessed memory, executive functions, attention, psychomotor speed, language, and manual dexterity. Participants with prediabetes had worse performances compared with those who had normal glycemia in 5 tests. The longitudinal analysis of the association between glycemia status at baseline and change in cognitive performances over 2-year follow-up (n = 283) suggested that patients with diabetes also showed a slightly higher decline on 5 of the 10 tests, those involving executive functions and memory functioning. Glycemia status at baseline was not significantly associated with NCI severity in cross-sectional (p = 0.44) and longitudinal (p = 0.64) analyses. In this hospital-based cohort of people living with HIV, diabetes, but not the other cardiovascular risk factors, is associated with worse cognitive performances in several cognitive domains and with larger decline in fewer domains over the short term. © 2015 American Academy of Neurology.
    No preview · Article · Jul 2015 · Neurology

  • No preview · Article · Jul 2015
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    ABSTRACT: Introduction: Few recent studies have suggested declining trends in dementia frequency. French cohorts with long follow-up allowed us to explore incidence evolution trends. Methods: Two different populations of subjects aged ≥65 years included in 1988-1989 (n = 1469) and 1999-2000 (n = 2104) were followed up over 10 years, with systematic assessment for cognition and dementia. Multistates illness-death models were used to compare dementia incidence using both clinical and algorithmic diagnoses. Results: Using the algorithmic diagnosis, incidence declined significantly overall and for women (age-adjusted hazard ratio [HR] = 0.62; confidence interval [CI] = 0.48-0.80 for women between the two populations). Differences in education, vascular factors, and depression accounted only to some extent for this reduction (women full-adjusted HR = 0.73; CI = 0.57-0.95). No significant decreasing trends were found for men or when using the clinical diagnosis for either sex. Discussion: Our study provides further support for a decrease in dementia incidence between the 1990s and the 2000s. Changes in diagnostic boundaries mask this reduction.
    Full-text · Article · Jul 2015 · Alzheimer's & dementia: the journal of the Alzheimer's Association

  • No preview · Article · Jul 2015

Publication Stats

8k Citations
1,495.01 Total Impact Points

Institutions

  • 2005-2015
    • French Institute of Health and Medical Research
      • Epidemiology and Biostatistics Center
      Lutetia Parisorum, Île-de-France, France
  • 2000-2015
    • Université Victor Segalen Bordeaux 2
      • Institut de Santé Publique d'Epidémiologie et de Développement (ISPED)
      Burdeos, Aquitaine, France
  • 1998-2015
    • University of Bordeaux
      Burdeos, Aquitaine, France
  • 1990-2015
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 2012-2014
    • Bordeaux School of Public Health
      Burdeos, Aquitaine, France
    • Centre Hospitalier Universitaire de Bordeaux
      Burdeos, Aquitaine, France
  • 2010
    • Lille Catholic University
      Lille, Nord-Pas-de-Calais, France