3C Study Research Articles

Sleep complaints and cardio-cerebrovascular diseases in the elderly: A 6-year prospective study

Introduction While sleep disturbances may contribute to the development of cardio- cerebrovascular diseases (CVD), few studies have examined the association of sleep complaints (insomnia complaints and excessive daytime sleepiness (EDS)) with history of CVD and incident CVD in persons over 65. Materials and methods CVD was assessed at baseline and at the two, four, and six-year follow-ups in 5494 non-demented subjects. Self-reported insomnia complaints (poor sleep quality, difficulty in initiating sleep, difficulty in maintaining sleep, and early morning awakening), EDS and sleep medication use were evaluated at baseline. Logistic regression models and Cox proportional hazard models, with delayed entry and age of participants as the time scale, were adjusted for socio-demographic, lifestyle and clinical variables. Results At baseline, 748 participants had a past-history of CVD which was associated with EDS (OR = 1.28 95% CI = [1.05–1.57]) and the number of insomnia complaints (OR = 1.26 95% CI = [1.03–1.55] for 1–2 insomnia complaints; OR = 1.32 95% CI = [1.03–1.71] for >2 complaints). In longitudinal analyses, neither the four components of insomnia nor the number of insomnia complaints were significantly associated with first or recurrent CVD events (n = 391 events). EDS was independently associated with future CVD events even after adjusting for prescribed sleep medication and past-history of CVD (HR = 1.35 95% CI = [1.06–1.71]). Conclusion Our results suggest a complex relationship between sleep complaints and CVD. Insomnia complaints are more likely to be a consequence of CVD, whereas EDS appears to be a determinant of CVD independently of past-history of CVD. EDS screening may thus constitute a means of detecting persons at high risk of CVD. Acknowledgements The 3C Study is conducted under a partnership agreement between Inserm, the Bordeaux II University and Sanofi- Synthelabo and was supported by the FRM, the CNMTS, DGS, MGEN, Institut de la Longevite, AFSSPS, the Regional Governments of Aquitaine, Bourgogne and Languedoc-Roussillon and, the Fondation de France, the Ministry of Research-Inserm Programme Cohorts and collection of biological material). The Lille received a grant from Eisai. Part of this project is financed by two grants from the ANR.

Gender Differences in the Association between Socioeconomic Status and Subclinical Atherosclerosis

ObjectivesThis study explored the pattern of associations between socioeconomic status (SES) and atherosclerosis progression (as indicated by carotid intima media thickness, CIMT) across gender.DesignCross-sectional analysis of a sample of 5474 older persons (mean age 73 years) recruited between 1999 and 2001 in the 3C study (France). We fitted linear regression models including neighborhood SES, individual SES and cardiovascular risk factors.ResultsCIMT was on average 24 µm higher in men (95% CI: 17 to 31). Neighborhood SES was inversely associated with CIMT in women only (highest versus lowest tertiles: −12.2 µm, 95%CI −22 to −2.4). This association persisted when individual SES and risk factors were accounted for. High individual education was associated with lower CIMT in men (−21.4 µm 95%CI −37.5 to −5.3) whereas high professional status was linked to lower CIMT among women (−15.7 µm 95%CI: −29.2 to −2.2). Adjustment for cardiovascular risk factors resulted in a slightly more pronounced reduction of the individual SES-CIMT association observed in men than in women.ConclusionIn this sample, neighborhood and individual SES displayed different patterns of associations with subclinical atherosclerosis across gender. This suggests that the causal pathways leading to SES variations in atherosclerosis may differ among men and women.

Minimising paper: electronic data capture methods in the 3c study

Methods In order to recruit at least 800 patients with minimum disruption to their clinical care a bespoke web-based case report form was developed which allows direct data entry by clinicians during routine clinic visits. Access to the web-based system is secure and randomization was conducted online after collection of a small number of data items to allow minimization. Data are verified at entry to avoid missing or impossible data which reduces the requirement for subsequent checks. In addition to data collected during study visits and annual postal questionnaires, all participants are flagged with national registries which capture all data of interest. The UK Transplant registry provides data to verify baseline characteristics and transplant survival; the UK Renal Registry provides transplant function information; the NHS Information Centre provides cancer and causespecific mortality data and Hospital Episode Statistics provides information on hospitalisations. Such follow-up provides unbiased, comprehensive follow-up information at very low-cost for the lifetime of the participants which allows the 3C Study to provide uniquely reliable information.

Constraining the location of rapid gamma-ray flares in the flat spectrum radio quasar 3C 273

We present a \gamma-ray photon flux and spectral variability study of the flat-spectrum radio quasar 3C 273 over a rapid flaring activity period between September 2009 to April 2010. Five major flares are observed in the source during this period. The most rapid flare observed in the source has a flux doubling time of 1.1 hr. The rapid \gamma-ray flares allow us to constrain the location and size of the \gamma-ray emission region in the source. The \gamma \gamma-opacity constrains the Doppler factor, $\delta_{\gamma} \geq$ 10 for the highest energy (15 GeV) photon observed by the {\it Fermi}-Large Area Telescope (LAT). Causality arguments constrain the size of the emission region to 1.6$\times 10^{15}$ cm. The \gamma-ray spectra measured over this period show clear deviations from a simple power law with a break in 1-2 GeV energy range. We discuss possible explanations for the origin of the \gamma-ray spectral breaks. Our study suggests that the \gamma-ray emission region in 3C 273 is located within the broad line region ($<$1.6 pc). The spectral behavior and temporal characteristics of the individual flares indicate the presence of multiple shock scenarios at the base of the jet.

Prospective analysis of the association between estrogen receptor gene variants and the risk of cognitive decline in elderly women

A plethora of data suggests a role for estrogen in cognitive function and genetic variants in the estrogen receptors ESR1 and ESR2 have been implicated in a range of hormone-sensitive diseases. It remains unknown however, whether ESR polymorphisms are associated with the risk of decline in specific domains of cognitive function. Data came from 3799 non-demented, community-dwelling elderly women recruited in France to the 3C Study. A short cognitive test battery was administered at baseline and 2, 4 and 7 years follow-up to assess global function, verbal fluency, visual memory, psychomotor speed and executive function. Detailed socio-demographic, behavioral, physical and mental health information was also gathered and genotyping of five common ESR1 and ESR2 polymorphisms was also performed. In multivariable-adjusted Cox analysis, ESR1 rs2234693 and rs9340799 were not significantly associated with the risk of decline on any of the cognitive tasks. However, significant associations with ESR2 polymorphisms were identified. The A allele of rs1256049 was associated with an increased risk of substantial decline in visual memory (HR:1.64, 95% CI: 1.23–2.18, p=0.0007), psychomotor speed (HR:1.43, 95% CI: 1.12–1.83, p=0.004), and on the incidence of Mild Cognitive Impairment (HR:1.31, 95% CI: 1.05–1.64, p=0.02). There was also a weaker association between the A allele of rs4986938 and a decreased risk of decline in psychomotor speed. Our large multicentre prospective study provides preliminary evidence that ESR2 genetic variants may be associated with specific cognitive domains and suggests that further examination of the role of this gene in cognitive function is warranted.

Dry eye disease in French elderly subjects: the Alienor Study

To describe dry eye disease in French elderly subjects. The Alienor Study is a population-based study on age-related eye disease in 963 residents of Bordeaux (France), aged 73 years or more. Self-reported dry eye disease and use of artificial tears were documented through face-to-face interview. Dry eye symptoms were assessed using the Ocular Surface Disease Index (OSDI) questionnaire and tear film stability by tear break-up time measurements (TBUT). Definite dry eye disease was defined as self-reported dry eye, confirmed by use of artificial tears and/or OSDI greater or equal to 22. Nine hundred and fifteen subjects, with mean age of 80 ± 4 years, returned the OSDI questionnaire. Of these, 271 (29.6%) subjects reported a dry eye disease and 135 (14.7%) were using artificial tears. An OSDI score > 22 was found in 359 (39.2%) subjects and a TBUT < 5 seconds in 335/746 (44.9%) subjects. Overall, definite dry eye affected 21.9% of subjects and was more frequent in women (27.1%) than in men (13.6%). After multivariate adjustment, dry eye disease was also significantly less frequent in subjects with high educational level (odds ratio (OR) = 0.49, 95% confidence interval (CI): 0.31-0.78 for long secondary school) and more frequent in subjects with ocular hypertension (OR = 1.61, 95% CI: 1.02-2.57) and those using anxiolytics (OR = 1.53, 95% CI: 1.02-2.29). This large observational study confirmed the high prevalence of dry eye symptoms among elderly subjects and confirmed some of the previously identified risk factors (in particular female gender and use of anxiolytics).

Campath, calcineurin inhibitor reduction and chronic allograft nephropathy (3C) study: background, rationale, and study protocol

BackgroundKidney transplantation is the best treatment for patients with end-stage renal failure, but uncertainty remains about the best immunosuppression strategy. Long-term graft survival has not improved substantially, and one possible explanation is calcineurin inhibitor (CNI) nephrotoxicity. CNI exposure could be minimized by using more potent induction therapy or alternative maintenance therapy to remove CNIs completely. However, the safety and efficacy of such strategies are unknown.Methods/DesignThe Campath, Calcineurin inhibitor reduction and Chronic allograft nephropathy (3C) Study is a multicentre, open-label, randomized controlled trial with 852 participants which is addressing two important questions in kidney transplantation. The first question is whether a Campath (alemtuzumab)-based induction therapy strategy is superior to basiliximab-based therapy, and the second is whether, from 6 months after transplantation, a sirolimus-based maintenance therapy strategy is superior to tacrolimus-based therapy. Recruitment is complete, and follow-up will continue for around 5 years post-transplant. The primary endpoint for the induction therapy comparison is biopsy-proven acute rejection by 6 months, and the primary endpoint for the maintenance therapy comparison is change in estimated glomerular filtration rate from baseline to 2 years after transplantation. The study is sponsored by the University of Oxford and endorsed by the British Transplantation Society, and 18 centers for adult kidney transplant are participating.DiscussionLate graft failure is a major issue for kidney-transplant recipients. If our hypothesis that minimizing CNI exposure with Campath-based induction therapy and/or an elective conversion to sirolimus-based maintenance therapy can improve long-term graft function and survival is correct, then patients should experience better graft function for longer. A positive outcome could change clinical practice in kidney transplantation. Trial registrationClinicalTrials.gov, NCT01120028 and ISRCTN88894088

Estrogen receptor polymorphisms and incident dementia: The prospective 3C study

BackgroundGenetic variation in the estrogen receptor (ESR) may be associated with the incidence of Alzheimer's disease (AD), but this association could be modified by genetic and environmental factors. MethodsThe association between five ESR α (ESR1) and β (ESR2) polymorphisms with 7-year dementia incidence was examined among 6959 older men and women from the Three City Study using multivariate-adjusted Cox regression models with delayed entry. Gender, the apolipoprotein E (APOE) ε4 allele, and hormone treatment were considered as potential effect modifiers of this association. ResultsAmong women, the CC genotype of ESR1rs2234693 was specifically associated with a small increased risk of AD (adjusted hazard ratio [HR]: 1.54, 95% confidence interval [CI]: 1.03–2.28, P = .03). However, women with this genotype had a substantially increased risk of AD associated with the APOE ε4 allele (adjusted HR: 3.24, 95% CI: 1.81–5.79 for women rs2234693 CC; compared with HR: 1.87, 95% CI: 1.37–2.56 for all women). There was also evidence of a nominally significant interaction between the ESR1 and ESR2 polymorphisms on the risk of all dementias (P = .04). Hormone treatment did not modify these associations, and there were no significant associations in men. ConclusionsAlthough there was only weak support for a gender-specific association between the common ESR1rs2234693 polymorphism and AD, this polymorphism may act as an effect modifier, modifying the association between an ESR2 polymorphism and dementia, as well as the risk of AD associated with the APOE ε4 allele.

Modeling of Oxidized PTH (oxPTH) and Non-oxidized PTH (n-oxPTH) Receptor Binding and Relationship of Oxidized to Non-Oxidized PTH in Children with Chronic Renal Failure, Adult Patients on Hemodialysis and Kidney Transplant Recipients

Background: The biological properties of oxidized and non-oxidized PTH are substantially different. Oxidized PTH (oxPTH) loses its PTH receptor-stimulating properties, whereas non-oxidized PTH (n-oxPTH) is a full agonist of the receptor. This was described in more than 20 well published studies in the 1970^s and 80^s. However, PTH oxidation has been ignored during the development of PTH assays for clinical use so far. Even the nowadays used third generation assay systems do not consider oxidation of PTH We recently developed an assay to differentiate between oxPTH and n-oxPTH. In the current study we established normal values for this assay system. Furthermore, we compare the ratio of oxPTH to n-oxPTH in different population with chronic renal failure: 620 children with renal failure stage 2-4 of the 4C study, 342 adult patients on dialysis, and 602 kidney transplant recipients. In addition, we performed modeling of the interaction of either oxPTH or n-oxPTH with the PTH receptor using biophysical structure approaches. Results: The children had the highest mean as well as maximum n-oxPTH concentrations as compared to adult patients (both patients on dialysis as well as kidney transplant recipients). The relationship between oxPTH and n-oxPTH of individual patients varied substantially in all three populations with renal impairment. The analysis of n-oxPTH in 89 healthy control subjects revealed that n-oxPTH concentrations in patient with renal failure were higher as compared to healthy adult controls (2.25-fold in children with renal failure, 1.53-fold in adult patients on dialysis, and 1.56-fold in kidney transplant recipients, respectively). Computer assisted biophysical structure modeling demonstrated, however, minor sterical- and/or electrostatic changes in oxPTH and n-oxPTH. This indicated that PTH oxidation may induce refolding of PTH and hence alters PTH-PTH receptor interaction via oxidation induced three-dimensional structure alteration of PTH. Conclusion: A huge proportion of circulating PTH measured by current state-of-the-art assay systems is oxidized and thus not biologically active. The relationship between oxPTH and n-oxPTH of individual patients varied substantially. Non-oxidized PTH concentrations are 1.5 - 2.25 fold higher in patients with renal failure as compared to health controls. Measurements of n-oxPTH may reflect the hormone status more precise. The iPTH measures describes most likely oxidative stress in patients with renal failure rather than the PTH hormone status. This, however, needs to be demonstrated in further clinical studies.

From Genetics to Dietetics: The Contribution of Epidemiology to Understanding Alzheimer's Disease

Late-life dementia results from non-modifiable risk factors such as age and genetics, modulated by deleterious and protective environmental factors among which nutrition may play a major role. This paper highlights five major recent contributions of the French Three-City (3C) and PAQUID epidemiological studies to Alzheimer's disease (AD) knowledge, targeting genetic and dietary risk factors, and the impact of cognitive decline in daily living. The 3C study contributed to a large genome-wide association study to identify new genetic risk factors for AD. In addition to apolipoprotein E (APOE), two loci gave replicated evidence of association: one within CLU, encoding clusterin or apolipoprotein J, and the other within CR1, encoding the complement component receptor 1. Although the attributable fraction of risk for these polymorphisms is moderate, genetic studies provide significant insights into the molecular bases of AD. Regarding dietary data, findings from 3C suggest that healthy diets associating sources of both omega 3 fatty acids (fish) and antioxidants (fruits and vegetables) such as the Mediterranean diet, and caffeine could be associated with decreased risk for AD. However, the protective effect of omega3 fatty acids might be limited to APOE4 non-carriers. Future research should focus on gene-nutrient interactions. Regarding the functional impact of prodromal AD, the PAQUID study showed that taking into account mild functional limitations considerably increases the predictive value of neuropsychological tests for conversion to dementia. Research should focus on sensitive instruments to capture early functional decline to improve the identification of elderly patients at high risk of conversion to dementia.

Nutrient patterns and risk of fracture in older subjects: results from the Three-City Study

We investigated the association between nutrient patterns and risk of fractures in 1,482 older subjects. Patterns associated with higher intakes of Ca, P, vitamin B12, proteins and unsaturated fats, and moderate alcohol intake, provided by diets rich in dairies and charcuteries, were related to a lower risk of wrist and hip fractures. The purpose of this study was to investigate the relationship between patterns of nutrient intake and the risk of fractures in older subjects. Among 1,482 participants from the Bordeaux sample of the Three-City (3C) Study who completed a 24-h dietary recall and a food frequency questionnaire, we examined the association between patterns of nutrient intake derived from principal component analysis and 8-year incidence of self-reported fractures of the hip, the wrist, and the vertebrae. A "nutrient-dense" pattern rich in Ca and P, iron, vitamins B including B12, vitamins C and E, alcohol, proteins, and unsaturated fats, and characterized by a higher consumption of fruits and vegetables, meats and fish, cheese and milk, charcuteries, cereals, rice, pasta, and potatoes, was associated with a 19% (95% CI 2-34%, P=0.03) lower risk of wrist fractures. The same pattern was associated with a 14% (95% CI 2-25%) lower risk of fractures at any site. A "south-western French" pattern rich in Ca, P, vitamins D and B12, retinol, alcohol, proteins, and fats-including unsaturated fats; poor in vitamins C, E, and K, carotenes, folates, and fibers; and related to a higher consumption of cheese, milk, and charcuterie and a lower consumption of fruits and vegetables was related to a 33% lower risk of hip fractures (95% CI 3-39%, P=0.03). Higher intakes of Ca, P, vitamin B12, proteins, and unsaturated fats and moderate alcohol, provided by dietary patterns rich in cheese, milk, and charcuteries, were related to a lower risk of wrist and hip fractures in our cohort.

Analysis of long-range chromatin interactions using Chromosome Conformation Capture

Chromosome Conformation Capture, or 3C, is a pioneering method for investigating the three-dimensional structure of chromatin. 3C is used to analyze long-range looping interactions between any pair of selected genomic loci. Most 3C studies focus on defined genomic regions of interest that can be up to several hundred Kb in size. The method has become widely adopted and has been modified to increase throughput to allow unbiased genome-wide analysis. These large-scale adaptations are presented in other articles in this issue of Methods. Here we describe the 3C procedure in detail, including the appropriate use of the technology, the experimental set-up, an optimized protocol and troubleshooting guide, and considerations for data analysis. The protocol described here contains previously unpublished improvements, which save time and reduce labor. We pay special attention to primer design, appropriate controls and data analysis. We include notes and discussion based on our extensive experience to help researchers understand the principles of 3C-based techniques and to avoid common pitfalls and mistakes. This paper represents a complete resource and detailed guide for anyone who desires to perform 3C.

Clinical usefulness of the metabolic syndrome for the risk of coronary heart disease does not exceed the sum of its individual components in older men and women. The Three-City (3C) Study

ObjectivesTo investigate the respective associations and clinical usefulness of the metabolic syndrome (MetS) and its individual components to predict the risk of first coronary heart disease (CHD) events in elderly.DesignThe...

Single polymorphism nucleotide rs1333049 on chromosome 9p21 is associated with carotid plaques but not with common carotid intima-media thickness in older adults. A combined analysis of the Three-City and the EVA studies

ObjectivesTo address the relationship of rs1333049, the 9p21 variant showing the strongest association with coronary heart disease (CHD), with carotid plaques and plaque-free common carotid artery intima-media thickness (CCA-IMT) in older adults from 2 French population-based cohorts. MethodsWe genotyped for rs1333049, 4097 CHD-free participants including 3191 aged 65–86 years from the Three-City (3C) Study and 906 aged 59–71 years from the Vascular Aging Study (EVA). Plaque-free mean CCA-IMT and the presence of carotid plaques were assessed. ResultsIn multivariate analysis, each C allele copy of rs1333049 was associated with baseline carotid plaques (odds ratio (OR)=1.24; 95% confidence interval (CI)=1.13–1.36; p<0.001) but not with baseline CCA-IMT (p=0.19). Among the EVA participants, the C allele was associated with 4-year plaques progression (p=0.04) but not with CCA-IMT progression. ConclusionThe chromosome 9p21 locus might influence CHD risk through carotid plaques development.

Abdominal Obesity and Late‐Onset Asthma: Cross‐Sectional and Longitudinal Results: The 3C Study

Whereas global obesity assessed by BMI has been related to asthma risk, little is known as to the potential implication of abdominal adiposity in this relationship. In the elderly, in whom asthma remains poorly studied, abdominal adiposity tends to increase at the expense of muscle mass. The purpose of this study was to investigate the association between abdominal adiposity, assessed by waist circumference (WC), and prevalence and incidence of asthma in a large elderly cohort. Cross-sectional analysis was based on 7,643 participants aged ≥65 years including 592 (7.7%) with lifetime physician-diagnosed asthma. Longitudinal analysis involved 6,267 baseline nonasthmatics followed-up for a period of 4 years, 67 of whom exhibited incident asthma. Baseline WC was categorized according to sex-specific criteria (men/women): <94/80 cm (reference), [94-102[/[80-88[ (abdominal overweight), and ≥102/88 (abdominal obesity). Logistic and Cox regression models estimated asthma risk associated with WC after adjustment for age, sex, educational level, smoking status, BMI, physical ability, dyspnea, chronic bronchitis symptoms and history of cardiovascular disease. At baseline, asthma risk increased with increasing WC independently of BMI and other confounders (adjusted odds ratio (ORa), 95% confidence interval (CI): 1.30, 1.02-1.65 and ORa: 1.76, 1.31-2.36 for abdominal overweight and obesity, respectively). Asthma incidence was related to WC (hazard ratio (HRa), 95% CI: 2.69, 1.21-5.98 and HRa: 3.84, 1.55-9.49, for abdominal overweight and obesity, respectively). Estimates were similar in both sexes. In the elderly, abdominal adiposity was independently associated with increased prevalence and incidence of asthma. Studies aiming to understand the mechanisms involved in the adiposity-asthma link are needed.

The 3C Study: Coverage cost and care of type 1 diabetes in China—Study design and implementation

Aim To describe coverage, cost and care of type 1 diabetes (T1D) in 2 regions of China – Beijing and Shantou – including: Estimating the numbers of people with T1D diabetes. Estimating the economic burden of T1D and financial barriers to care. Identifying scale of necessary government investment to improve health care coverage. Defining the burden of disease based on clinical outcomes. Describing the education and care experience of people with T1D with comparison to selected clinical practice guidelines. Describing the information processes associated with diabetes care and education. Methods This is a mixed-methods descriptive study with three arms – coverage, cost and care. It is taking place in 4 tertiary hospitals, 3 secondary hospitals and 4 primary health facilities in Beijing, and 2 tertiary hospitals, 2 secondary hospitals and 2 primary health centres in Shantou, China. Two additional hospitals are involved in the coverage arm of the study. T1D participants are recruited from a 3-year list generated by each hospital and from those attending the outpatient clinic or admitted to the inpatient ward. Participants also include health care professionals and government officials. To determine coverage of care, a list of people with T1D is being developed including information on diagnosis, age, sex and vital status. The age and sex distribution will be compared with the expected distribution. To estimate the economic burden of T1D three groups of costs will be calculated – direct medical costs, direct non-medical costs and indirect costs from different perspectives of analysis (patients and their families, health system, insurer and societal perspective). The data are being collected from people with T1D (patient–parents face-to-face interviews), hospital billing departments, medical records and government officials using a combined “top-down, bottom-up” approach developed to validate the data. Quality of life is assessed using the EQ-5D tool and burden of disease is measured based on clinical outcomes and complications. Standard care will be defined, costed and compared to the cost of current care identified within the study to determine the investment required to improve outcomes. The third arm includes three components – health policy, clinical care and education, and information management. Face-to-face, semi-structured interviews are conducted with people with T1D (for those <15 years of age parents are interviewed), health care professionals, senior hospital management and government officials. The core Summary of Diabetes Self-Care Activities Measure plus an additional 6 questions from the revised SDSCA scale are used to assess patient self-care. A medical records audit tool is used to assess care [7]. Clinical outcomes and self-care activities will be analysed for associations with care and education. Information management and care processes will be described using the Standard for Integration Definition for Function Modelling (IDEF0) [8]. Progress to date At the time of writing (early October) the 3-year case list includes 1269 people with type 1 diabetes from Beijing and 481 people for Shantou, a total of 1750. In addition, two hundred and twenty people with T1D or their parents participated in face-to-face interviews in Beijing and 183 in Shantou, a total of 403. Practical preliminary conclusions Key implementation considerations were identified early in the project. Project success is dependent on strong local partnerships with local opinion leaders and key officials. It is important that a physician is the first point of contact to build the case list and recruit participants. July, August and January are peak months for recruiting school-age children in the Children's Hospital as this is school vacation period when they are more likely to attend clinics.

Editor's Note: Self-rated health and risk of incident dementia: A community- based elderly cohort, the 3C Study

In this study by Montlahuc et al.,1 the authors explore associations between self-rated health and subsequent dementia. Self-perceptions of health status might include insights …

Self-rated health and risk of incident dementia

We examined the relationship between self-rated health and incident dementia, and investigated the impact of cognitive complaints, depressive symptoms, and functional status on this relationship. Participants of the 3C Study, a prospective cohort study composed of 8,169 community-dwelling persons aged ≥65 years, were asked to rate their health at the baseline examination in 1999-2001. They were followed for a median of 6.7 years during which dementia was screened and diagnosed. Hazard ratios (HR) of dementia according to baseline self-rated health (good, fair, or poor) were estimated with a Cox model adjusted for potential confounders. During the 46,990 person-years of follow-up, 618 participants developed dementia. Risk of dementia was increased in participants with poor (adjusted HR 1.70, 95% confidence interval [CI] 1.22-2.37) or fair (adjusted HR 1.34, 95% CI 1.13-1.59) self-rated health compared to those with good self-rated health. Poor self-rated health was associated with both AD (1.48, 1.00-2.24) and vascular dementia (3.38, 1.25-9.17). Self-rated health was a stronger predictor of dementia in participants without cognitive complaints (risk of dementia in subjects without cognitive complaints rating their health as poor: 1.96 [1.24-3.09], p = 0.004) and in those without functional disability. Participants rating their health as poor or fair at baseline were at increased risk of incident dementia during follow-up. Self-rated health could help raise awareness of medical doctors about a patient's risk of dementia, especially in those without conditions indicative of potential cognitive impairment.

Depression history, depressive symptoms and incident dementia: The 3C study

Depression and dementia are highly prevalent conditions among elderly but the nature of their relationship remains a matter of debate. The aim of our study was to investigate whether depression assessed by different markers predicts the risk of incident dementia in elderly individuals. Data was derived from the 3C cohort study conducted in community-dwelling individuals aged 65 years and over, randomly recruited from electoral rolls of three French areas and followed up for four years (1999-2001 through 2004) with assessments every 2 years. The study sample comprised 7989 dementia-free individuals (mean age, 74.0 years; 61% women) assessed at baseline for current or past Major Depressive Episodes (MDE) based on MDE module of the Mini International Neuropsychiatric Interview, self-reported lifetime treated depression, and level of depressive symptoms using the Center for Epidemiologic Studies-Depression (CES-D) Scale. Fully adjusted Cox proportional hazards models were applied to examine the risk of incident dementia associated with these markers of depression. MDE and self-reported lifetime treated depression did not increase incident dementia risk. Conversely, high level of depressive symptoms at baseline was associated with a 50% increased risk of dementia (adjusted Hazard Ratio [HR], 1.5; 95% Confidence interval [CI], 1.2-2.2). This result was driven by a five-fold increased risk of vascular dementia (HR, 4.8; 95% CI, 2.2-10.7; p < 0.0001), whereas there was no increased risk of Alzheimer disease (1.0; 0.7-1.6). In elderly individuals, high level of depressive symptoms is predictive of vascular dementia within a few years. This close temporal association suggests that depression is less a risk factor for than a prodromal symptom of vascular dementia. This should urge clinicians to reinforce monitoring of both depressive symptoms and subsequent cognitive decline and to control vascular factors to possibly slow down the dementing process. High Depressive Symptoms at baseline and risk of dementia by type

Self-Rated Health and Risk of Incident Dementia: A Community-Based Elderly Cohort, the 3C Study

Objectives: We examined the relationship between self-rated health and incident dementia, and investigated the impact of cognitive complaints, depressive symptoms, and functional status on this relationship. Methods: Participants of the 3C Study, a prospective cohort study composed of 8,169 community-dwelling persons aged ≥65 years, were asked to rate their health at the baseline examination in 1999–2001. They were followed for a median of 6.7 years during which dementia was screened and diagnosed. Hazard ratios (HR) of dementia according to baseline self-rated health (good, fair, or poor) were estimated with a Cox model adjusted for potential confounders. Results: During the 46,990 person-years of follow-up, 618 participants developed dementia. Risk of dementia was increased in participants with poor (adjusted HR 1.70, 95% confidence interval [CI] 1.22–2.37) or fair (adjusted HR 1.34, 95% CI 1.13–1.59) self-rated health compared to those with good self-rated health. Poor self-rated health was associated with both AD (1.48, 1.00–2.24) and vascular dementia (3.38, 1.25–9.17). Self-rated health was a stronger predictor of dementia in participants without cognitive complaints (risk of dementia in subjects without cognitive complaints rating their health as poor: 1.96 [1.24–3.09], p = 0.004) and in those without functional disability. Conclusions: Participants rating their health as poor or fair at baseline were at increased risk of incident dementia during follow-up. Self-rated health could help raise awareness of medical doctors about a patient9s risk of dementia, especially in those without conditions indicative of potential cognitive impairment.