Publications by authors named "Annick Alpérovitch"

86 Publications

[Ethics of clinical trials].

Med Sci (Paris) 2020 Apr 1;36(4):303-307. Epub 2020 May 1.

Directeur de recherche honoraire à l'Inserm Ancien Directeur général de l'Inserm.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1051/medsci/2020092DOI Listing
April 2020

Association Between Cerebral Small Vessel Disease With Antidepressant Use and Depression: 3C Dijon Magnetic Resonance Imaging Study.

Stroke 2020 02 12;51(2):402-408. Epub 2019 Dec 12.

From the Inserm, Bordeaux Population Health Research Center, UMR 1219 (P.J.T., A.A., A.S., S.D., C.T.), University of Bordeaux, France.

Background and Purpose- Evidence links antidepressant use with cerebral small vessel disease; however, it remains unclear whether people with depression face comparable risk. This study aims to determine the association between antidepressant drug use and depression with markers of cerebral small vessel disease. Methods- One thousand nine hundred five participants (mean age, 72.5 years; 60% women) without stroke or dementia history underwent brain magnetic resonance imaging at baseline, and 1402 individuals underwent a second magnetic resonance imaging at 4 years. Outcomes were lacunes 3 to 15 mm and white matter hyperintensity volume (cm) at baseline and follow-up. Exposure to antidepressants was grouped as (1) selective serotonin reuptake inhibitors (n=68), (2) tricyclics (n=40), (3) atypicals (n=24), (4) depressed nonusers (n=303), and (5) nondepressed/nonuser group (reference group, n=1470). Statistical analyses adjusted for propensity scores due to the nonrandomized exposure to antidepressant drugs. Results- There was an association between use of atypical antidepressants with lacunes at baseline (adjusted rate ratio, 2.59 [95% CI, 1.14-5.88]; =0.023) and follow-up (adjusted rate ratio, 3.05 [95% CI, 1.25-7.43]; =0.014). Lacunes at baseline were also associated with depressed nonusers (adjusted rate ratio, 1.53 [95% CI, 1.06-2.21]; =0.023). Selective serotonin reuptake inhibitor users and depressed nonusers displayed higher total, periventricular, and deep white matter hyperintensity volumes at baseline. Selective serotonin reuptake inhibitor users had higher deep white matter hyperintensity volumes at follow-up. Conclusions- Users of atypical antidepressants, selective serotonin reuptake inhibitors, and depressed people without any antidepressant exposure all displayed markers of cerebral small vessel disease higher than the nondepressed/nonuser group. The findings suggest that cerebral small vessel disease is associated with depression and exposure to antidepressants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.119.026712DOI Listing
February 2020

Benzodiazepine, psychotropic medication, and dementia: A population-based cohort study.

Alzheimers Dement 2016 05 18;12(5):604-13. Epub 2015 Nov 18.

Inserm Research Center for Epidemiology and Biostatistics (U897) - Team Neuroepidemiology, Bordeaux, France; University of Bordeaux, Bordeaux, France. Electronic address:

Introduction: 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).

Discussion: Results of this large, prospective study show increased risk of dementia for long half-life benzodiazepine and psychotropic use.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jalz.2015.10.006DOI Listing
May 2016

Usefulness of data from magnetic resonance imaging to improve prediction of dementia: population based cohort study.

BMJ 2015 Jun 22;350:h2863. Epub 2015 Jun 22.

Inserm Research Centre for Epidemiology and Biostatistics (U897), Team Neuroepidemiology, F-33000 Bordeaux, France University of Bordeaux, College of Health Sciences, F-33000 Bordeaux, France

Objective: To determine whether the addition of data derived from magnetic resonance imaging (MRI) of the brain to a model incorporating conventional risk variables improves prediction of dementia over 10 years of follow-up.

Design: Population based cohort study of individuals aged ≥ 65.

Setting: The Dijon magnetic resonance imaging study cohort from the Three-City Study, France.

Participants: 1721 people without dementia who underwent an MRI scan at baseline and with known dementia status over 10 years' follow-up.

Main Outcome Measure: Incident dementia (all cause and Alzheimer's disease).

Results: During 10 years of follow-up, there were 119 confirmed cases of dementia, 84 of which were Alzheimer's disease. The conventional risk model incorporated age, sex, education, cognition, physical function, lifestyle (smoking, alcohol use), health (cardiovascular disease, diabetes, systolic blood pressure), and the apolipoprotein genotype (C statistic for discrimination performance was 0.77, 95% confidence interval 0.71 to 0.82). No significant differences were observed in the discrimination performance of the conventional risk model compared with models incorporating data from MRI including white matter lesion volume (C statistic 0.77, 95% confidence interval 0.72 to 0.82; P=0.48 for difference of C statistics), brain volume (0.77, 0.72 to 0.82; P=0.60), hippocampal volume (0.79, 0.74 to 0.84; P=0.07), or all three variables combined (0.79, 0.75 to 0.84; P=0.05). Inclusion of hippocampal volume or all three MRI variables combined in the conventional model did, however, lead to significant improvement in reclassification measured by using the integrated discrimination improvement index (P=0.03 and P=0.04) and showed increased net benefit in decision curve analysis. Similar results were observed when the outcome was restricted to Alzheimer's disease.

Conclusions: Data from MRI do not significantly improve discrimination performance in prediction of all cause dementia beyond a model incorporating demographic, cognitive, health, lifestyle, physical function, and genetic data. There were, however, statistical improvements in reclassification, prognostic separation, and some evidence of clinical utility.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4476487PMC
http://dx.doi.org/10.1136/bmj.h2863DOI Listing
June 2015

Primary prevention with lipid lowering drugs and long term risk of vascular events in older people: population based cohort study.

BMJ 2015 May 19;350:h2335. Epub 2015 May 19.

INSERM, U897-Epidemiology and Biostatistics, Bordeaux, France Université de Bordeaux, Bordeaux, France

Objective: To determine the association between use of lipid lowering drugs (statin or fibrate) in older people with no known history of vascular events and long term risk of coronary heart disease and stroke

Design: Ongoing prospective population based cohort study recruited in 1999-2000, with five face-to-face examinations.

Setting: Random sample of community dwelling population aged 65 years and over, living in three French cities (Bordeaux, Dijon, Montpellier).

Participants: 7484 men and women (63%) with mean age 73.9 years and no known history of vascular events at entry. Mean follow-up was 9.1 years.

Main Outcome Measures: Adjusted hazard ratios of coronary heart disease and stroke in baseline lipid lowering drug users compared with non-users, calculated using multivariable Cox proportional hazard models adjusted for numerous potential confounding factors. Hazard ratios were estimated for use of any lipid lowering drug and for statin and fibrate separately.

Results: Lipid lowering drug users were at decreased risk of stroke compared with non-users (hazard ratio 0.66, 95% confidence interval 0.49 to 0.90); hazard ratios for stroke were similar for statin (0.68, 0.45 to 1.01) and fibrate (0.66, 0.44 to 0.98). No association was found between lipid lowering drug use and coronary heart disease (hazard ratio 1.12, 0.90 to 1.40). Analyses stratified by age, sex, body mass index, hypertension, systolic blood pressure, triglyceride concentrations, and propensity score did not show any effect modification by these variables, either for stroke or for coronary heart disease.

Conclusion: In a population based cohort of older people with no history of vascular events, use of statins or fibrates was associated with a 30% decrease in the incidence of stroke.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4437042PMC
http://dx.doi.org/10.1136/bmj.h2335DOI Listing
May 2015

Plasma lipids and cerebral small vessel disease.

Neurology 2014 Nov 15;83(20):1844-52. Epub 2014 Oct 15.

From the University of Bordeaux Ségalen (S.S., C.T., C.D., Y.Z., A.A., S.D.), INSERM U897 Neuroepidemiology, Bordeaux, France; Pekin Union Medical College Hospital (Y.Z.), China; Inserm U1061(C.B.), Montpellier; University Montpellier I (C.B.); University Pierre et Marie Curie-Paris 6 (A.A.); CNRS-CEA UMR5296 (F.C., B.M.), Université Bordeaux Segalen, Bordeaux; University of Versailles Saint-Quentin-en-Yvelines (S.D.); Department of Neurology (S.D.), Lariboisière Hospital, Paris; INSERM UMR S-1161 (S.D.), Paris 7 University, France; Department of Neurology (S.D.), Bordeaux University Hospital, Bordeaux; and Department of Neurology (S.D.), Boston University School of Medicine, Framingham Heart Study, Boston, MA.

Objectives: We examined the cross-sectional association between lipid fractions and 2 MRI markers of cerebral small vessel disease, white matter hyperintensity volume (WMHV) and lacunes, representing powerful predictors of stroke and dementia.

Methods: The study sample comprised 2,608 participants from the 3C-Dijon Study (n = 1,842) and the Epidemiology of Vascular Aging Study (EVA) (n = 766), 2 large French population-based cohorts (72.8 ± 4.1 and 68.9 ± 3.0 years; 60.1% and 58.4% women, respectively). Analyses were performed separately in each study and combined using inverse variance meta-analysis. Lipid fractions (triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol) were studied as continuous variables. WMHV was studied both in a continuous and dichotomous manner, the latter reflecting the age-specific top quartile of WMHV (EXT-WMHV). Analyses were adjusted for age and sex.

Results: Increasing triglycerides were associated with larger WMHV in the 3C-Dijon Study (β ± SE = 0.0882 ± 0.0302, p = 0.0035), in the EVA Study (β ± SE = 0.1062 ± 0.0461, p = 0.021), and in the combined analysis (β ± SE = 0.0936 ± 0.0252, p = 0.0002) and with higher frequency of lacunes in the 3C-Dijon Study (odds ratio [OR] = 1.65 [95% confidence interval 1.10-2.48], p = 0.015), in the EVA Study (OR = 1.58 [95% confidence interval 0.93-2.70], p = 0.09), and in the combined analysis (OR = 1.63 [95% confidence interval 1.18-2.25], p = 0.003). Associations were attenuated but maintained after adjusting for other vascular risk factors or for inflammatory markers. Associations were present and in the same direction both in participants taking and those not taking lipid-lowering drugs but tended to be stronger in the former for EXT-WMHV. Increasing low-density lipoprotein cholesterol tended to be associated with a decreased frequency and severity of all MRI markers of cerebral small vessel disease in both studies.

Conclusions: Increasing triglycerides but not other lipid fractions were associated with MRI markers of cerebral small vessel disease in older community persons.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000000980DOI Listing
November 2014

[Historical cohorts: contribution to epidemiological knowledge].

Bull Acad Natl Med 2013 Feb;197(2):293-7; discussion 297-8

Several large cohort studies have been performed in France since the 1960s. Participants were recruited from general or occupational populations. Whatever their primary objective, these cohort studies provided important data on the prevalence and risk factors of major public health problems. The scientific value of these studies, which gave rise to a very large numbers of publications, is internationally recognized.
View Article and Find Full Text PDF

Download full-text PDF

Source
February 2013

Older age at retirement is associated with decreased risk of dementia.

Eur J Epidemiol 2014 May 4;29(5):353-61. Epub 2014 May 4.

Centre INSERM U897-Epidemiologie-Biostatistique and CIC-EC7, INSERM, ISPED, 33000, Bordeaux, France,

To test the hypothesis that age at retirement is associated with dementia risk among self-employed workers in France, we linked health and pension databases of self-employed workers and we extracted data of those who were still alive and retired as of December 31st 2010. Dementia cases were detected in the database either through the declaration of a long-term chronic disease coded as Alzheimer's disease and other dementia (International Classification of Disease codes G30, F00, F01, F03) or through the claim for reimbursement of one of the anti-dementia drugs. Data were analyzed using Cox proportional hazard model adjusting for potential confounders. Among the 429,803 retired self-employed workers alive on December 31st 2010, prevalence of dementia was 2.65 %. Multivariable analyses showed that the hazard ratio of dementia was 0.968 [95 % confidence interval = (0.962-0.973)] per each extra year of age at retirement. After excluding workers who had dementia diagnosed within the 5 years following retirement, the results remained unchanged and highly significant (p < 0.0001). We show strong evidence of a significant decrease in the risk of developing dementia associated with older age at retirement, in line with the "use it or lose it" hypothesis. Further evidence is necessary to evaluate whether this association is causal, but our results indicate the potential importance of maintaining high levels of cognitive and social stimulation throughout work and retiree life.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10654-014-9906-3DOI Listing
May 2014

Gender differences in the association between socioeconomic status and subclinical atherosclerosis.

PLoS One 2013 25;8(11):e80195. Epub 2013 Nov 25.

French School of Public Health, Rennes, France.

Objectives: This study explored the pattern of associations between socioeconomic status (SES) and atherosclerosis progression (as indicated by carotid intima media thickness, CIMT) across gender.

Design: Cross-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.

Results: CIMT 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.

Conclusion: In 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0080195PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3839909PMC
January 2015

Intensity of human prion disease surveillance predicts observed disease incidence.

J Neurol Neurosurg Psychiatry 2013 Dec 21;84(12):1372-7. Epub 2013 Aug 21.

Australian National Creuztfeldt-Jakob Disease Registry, Department of Pathology, The University of Melbourne, , Parkville, Australia.

Background: Prospective national screening and surveillance programmes serve a range of public health functions. Objectively determining their adequacy and impact on disease may be problematic for rare disorders. We undertook to assess whether objective measures of disease surveillance intensity could be developed for the rare disorder sporadic Creutzfeldt-Jakob disease (CJD) and whether such measures correlate with disease incidence.

Method: From 10 countries with national human prion disease surveillance centres, the annual number of suspected prion disease cases notified to each national unit (n=17,610), referrals for cerebrospinal fluid (CSF) 14-3-3 protein diagnostic testing (n=28,780) and the number of suspect cases undergoing diagnostic neuropathological examination (n=4885) from 1993 to 2006 were collected. Age and survey year adjusted incidence rate ratios with 95% CIs were estimated using Poisson regression models to assess risk factors for sporadic, non-sporadic and all prion disease cases.

Results: Age and survey year adjusted analysis showed all three surveillance intensity measures (suspected human prion disease notifications, 14-3-3 protein diagnostic test referrals and neuropathological examinations of suspect cases) significantly predicted the incidence of sporadic CJD, non-sporadic CJD and all prion disease.

Conclusions: Routine national surveillance methods adjusted as population rates allow objective determination of surveillance intensity, which correlates positively with reported incidence for human prion disease, especially sporadic CJD, largely independent of national context. The predictive relationship between surveillance intensity and disease incidence should facilitate more rapid delineation of aberrations in disease occurrence and assessment of the adequacy of disease monitoring by national registries.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jnnp-2012-304820DOI Listing
December 2013

Trends in recognition and treatment of dementia in france analysis of the 2004 to 2010 database of the national health insurance plan.

Alzheimer Dis Assoc Disord 2013 Jul-Sep;27(3):213-7

INSERM U708-Neuroepidemiology, Université Pierre et Marie Curie-Paris6, Paris, France.

Dementia is considered as underdiagnosed. We examined whether the proportion of persons aged 65 years and older who had been diagnosed as demented has changed over a 7-year period. The study population was constituted by a cohort of about 70,000 persons who were representative of the French elderly covered by the national health care insurance plan. Data about all health care consumptions were extracted from the national insurance database. Patients using an antidementia drug, having a special dementia-related coverage status, or both were identified. Annual age-standardized and sex-standardized proportions of recognized dementia cases were estimated. Between 2004 and 2010, the overall standardized proportion of persons recognized as having dementia increased slightly but significantly (P<0.004) from 3.68% to 4.20%. The proportion of persons recognized as demented increased strongly with age. In 2010, it increased from 1.44% at age 70-74 to 10% at age more than 90 in men and from 1.30% to 17.0% in women. The proportion of cholinesterase inhibitor users decreased after the age of 85 years, whereas memantine use continued to increase. Our study suggested that, in 2010, >75% of the demented persons had been recognized and received pharmacological or/and nonpharmacological therapies for dementia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/WAD.0b013e3182695a3bDOI Listing
March 2014

Blood pressure variability and risk of dementia in an elderly cohort, the Three-City Study.

Alzheimers Dement 2014 Oct 15;10(5 Suppl):S330-7. Epub 2013 Aug 15.

INSERM, U708 Neuroepidemiology, Paris, France; University Bordeaux, Bordeaux, France. Electronic address:

Background: The relationship between blood pressure and dementia is incompletely understood in elderly individuals. Blood pressure variability may have a role in the risk of dementia.

Methods: This investigation was a cohort study of 6506 elderly individuals followed-up for 8 years (1999-2001 through 2008) with assessments at years 2, 4, and 7-8. Blood pressure was measured by electronic devices at baseline and at 2- and 4-year follow-up examinations. Cox proportional hazard models adjusted for potential confounders were used to estimate the risk of incident dementia according to blood pressure (means and coefficients of variation of the three measures).

Results: During the 40,151 person-years of follow-up 474 participants developed dementia. We observed no association between mean blood pressure and risk of dementia. In contrast, an increase of 1 standard deviation in the coefficient of variation of blood pressure was associated with a 10% increased risk of dementia. Analysis by deciles of the coefficient of variation showed that the higher the variability, the higher the risk of dementia (P<.02 for trend). In the fully adjusted Cox model, the risk of dementia for those in the highest decile of the coefficient of variation of systolic blood pressure was 1.77 (1.17-2.69) compared with the lowest decile.

Conclusions: In this cohort study, variability of blood pressure during follow-up was associated with an increased risk of incident dementia, whereas mean blood pressure was not. Limitation of blood pressure fluctuation may be an important target to preserve cognitive function in the elderly.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jalz.2013.05.1777DOI Listing
October 2014

Risk of breast cancer by individual insulin use: an international multicenter study.

Diabetes Care 2014 15;37(1):134-43. Epub 2013 Aug 15.

Corresponding author: Lamiae Grimaldi-Bensouda,

OBJECTIVE Several studies have been published in 2009 suggesting a possible association between insulin glargine and increased risk of malignancies, including breast cancer. The objective of this study was to assess the relation between the individual insulins (glargine, aspart, lispro, and human insulin) and development of breast cancer. RESEARCH DESIGN AND METHODS Seven hundred seventy-five incident cases of primary invasive or in situ carcinoma breast cancer occurring in women with diabetes from 92 centers in the U.K., Canada, and France were matched to a mean of 3.9 diabetic community control subjects (n = 3,050; recruited from 580 general practices) by country, age, recruitment date, and diabetes type and management. The main risk model was a multivariate conditional logistic regression model with case/control status as the dependent variable and individual insulin use, 8 years preceding the index date, as the independent variable, controlling for past use of any insulin, oral antidiabetes drugs, reproductive factors, lifestyle, education, hormone replacement therapy and history of contraceptive use, BMI, comorbidities, diabetes duration, and annual number of physician visits. Glargine was also compared with every other insulin by computing all ratios using the variance-covariance matrix of logistic model parameters. RESULTS Adjusted odds ratios of breast cancer for each type of insulin versus no use of that insulin were 1.04 (95% CI 0.76-1.44) for glargine, 1.23 (0.79-1.92) for lispro, 0.95 (0.64-1.40) for aspart, and 0.81 (0.55-1.20) for human insulin. Two-by-two comparisons found no difference between glargine and the different types of insulins. Insulin dosage or duration of use and tumor stage did not change the results. CONCLUSIONS This international study found no difference in the risk of developing breast cancer in patients with diabetes among the different types of insulin with short- to mid-term duration of use. Longer-term studies would be of interest.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2337/dc13-0695DOI Listing
August 2015

20-Year prevalence projections for dementia and impact of preventive policy about risk factors.

Eur J Epidemiol 2013 Jun 12;28(6):493-502. Epub 2013 Jun 12.

Inserm U897,ISPED, Université Bordeaux Ségalen, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France.

Incidence of dementia increases sharply with age and, because of the increase in life expectancy, the number of dementia cases is expected to rise dramatically over time. Some studies suggest that controlling some modifiable risk factors for dementia like diabetes or hypertension could lower its incidence. However, as treating these vascular factors would also reduce mortality risk, the actual impact of such public-health intervention on dementia prevalence is not known. Accounting for the impact of dementia and risk factors on mortality, the aim of this work was (1) to compute projections of age- and-sex specific prevalence of dementia in France from 2010 to 2030, (2) to evaluate how public-health interventions targeting risk factors for dementia could change these projections. Age-and-sex specific incidence of dementia and mortality of demented subjects were estimated from the Paquid population-based cohort using a semi-parametric illness-death model. Future global mortality rates and population sizes were obtained from national demographic projections. Under the assumption that life expectancy will increase by 3.5 years for men and 2.8 years for women by 2030, the number of subjects with dementia was estimated to increase by about 75% from 2010 to 2030 with a 200% increase after 90 years of age. Therapeutic intervention on the whole population reducing high blood pressure prevalence would lead to a decrease in both dementia incidence rates and mortality and would have a modest impact on the number of dementia cases. On the other hand, a preventive dementia treatment targeting ApoE4 carriers would probably not improve survival and hence would decrease dementia prevalence by 15-25%.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10654-013-9818-7DOI Listing
June 2013

Categories of hypertension in the elderly and their 1-year evolution. The Three-City Study.

J Hypertens 2013 Apr;31(4):680-9

INSERM, Neuroepidemiology, Bordeaux, France.

Objective: To assess the 1-year risk of developing sustained hypertension in untreated elderly with white-coat hypertension (WCHT) or masked hypertension (MHT), and the 1-year risk of developing uncontrolled hypertension in treated elderly with office or home uncontrolled hypertension (OUHT or HUHT).

Methods: We studied the 1-year risk of developing sustained or uncontrolled hypertension in a community-based cohort of 1481 individuals aged at least 73 years. The same BP device was used throughout the entire study. WCHT was defined as high blood pressure (BP) at office and normal home BP without antihypertensive intake, OUHT as high office BP and normal home BP with antihypertensive intake, MHT as high BP at home and normal office BP without antihypertensive intake, and HUHT as high home BP and normal office BP with antihypertensive intake. Sustained hypertension was defined as high office and home BP without antihypertensive intake and uncontrolled hypertension as high office and home BP with antihypertensive intake.

Results: Sustained or uncontrolled hypertension at 1 year was diagnosed in 13% of participants with high office BP and in 26% of those with high home BP. Compared to participants with normal office and home BP, risk of sustained/uncontrolled hypertension was increased about three-fold in individuals with high office BP [OR = 2.9; 95% confidence interval (CI) = 1.5-5.5; P = 0.002] and about seven-fold in those with high home BP (OR = 6.8; 95% CI = 3.8-12.2; P < 0.0001). These risks were higher in individuals not treated by antihypertensive (OR(WCHT) = 4.3, P = 0.03; OR(MHT) = 16.8, P < 0.0001).

Conclusion: In this community-based study, elderly individuals with high office or home BP had an increased risk of hypertension 1 year later. This risk was higher among individuals not treated by antihypertensive and particularly in those with MHT. As these high-risk individuals would be otherwise undetected our results strongly support the large use of home blood pressure measurement in the elderly.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/HJH.0b013e32835ee0caDOI Listing
April 2013

Feasibility of home blood pressure measurement in elderly individuals: cross-sectional analysis of a population-based sample.

Am J Hypertens 2012 Dec 16;25(12):1279-85. Epub 2012 Aug 16.

INSERM, Neuroepidemiology U708, Bordeaux, France.

Background: Home blood pressure measurement (HBPM) is recommended by hypertension guidelines, particularly in the elderly. However, feasibility of HBPM in this age group has not been fully established. Our objective was therefore to assess HBPM feasibility in elderly individuals of the general population.

Methods: After minimal training, 1,814 individuals aged ≥ 73 years were asked to measure their blood pressure (BP) at home six times per day (three in the morning and three in the evening) during 3 days, with the validated device OMRON M6 (exam 1). Measures of BP were self-reported by the participants on a booklet. The same procedure was applied 1-year later (exam 2). HBPM was considered as successful when at least 12 measures of the 18 were performed. Participants were also asked to complete a questionnaire intended to assess difficulties met performing HBPM.

Results: Rate of success for HBPM was 96% at exam 1 and 97% at exam 2. We analyzed pattern of individuals who failed HBPM examination and found that age >80, low education level, and non-autonomy were independently associated with an increased risk of HBPM failure. HBPM was considered nonrestrictive by 89% of participants and 97% declared that HBPM was simple to perform.

Conclusions: In this population-based sample of elderly, rate of success of HBPM was high and maintained at 1-year after minimal training. Moreover, HBPM acceptance was excellent. These results suggest that HBPM is feasible and can be largely diffused to the elderly of general population. However, particular care must be given to very old, nonautonomous, and low educated individuals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/ajh.2012.121DOI Listing
December 2012

From genetics to dietetics: the contribution of epidemiology to understanding Alzheimer's disease.

J Alzheimers Dis 2013 ;33 Suppl 1:S457-63

INSERM, U897, Bordeaux, France.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/JAD-2012-129019DOI Listing
June 2013

Preclinical sporadic Creutzfeldt-Jakob disease in French blood donors: an epidemiologic model-based study.

Transfusion 2012 Jun 1;52(6):1290-5. Epub 2011 Dec 1.

Institut de Veille Sanitaire, Saint-Maurice, France.

Background: A recent case-control study showed that transfusion recipients were at an increased risk of developing sporadic Creutzfeldt-Jakob disease (sCJD), suggesting that blood donors with silent preclinical sCJD could transmit the sCJD agent. We therefore estimated the annual number of French blood donors expected to have preclinical sCJD at the time of donation.

Study Design And Methods: We developed a mathematical model to estimate the number of blood donors who would subsequently develop sCJD, under various assumptions about how long their blood might be infective before clinical onset. The model used distributions by age group and sex for sCJD cases, blood donor population, French general population, and mortality in the general population.

Results: Using 1999 to 2008 data, modeling showed that, each year, a mean of 1.1 (standard deviation [SD], 0.3) donors were within 1 year of sCJD onset at the time of blood donation, 6.9 (SD, 0.5) donors were within 5 years, 18.0 (SD, 0.6) were within 10 years, and 33.4 (SD, 1.1) were within 15 years.

Conclusion: Few donors are expected to be in the late preclinical stage of sCJD at the time of blood donation. This result and that of the worldwide absence of any epidemic increase in sCJD over the years indicate that this risk of transfusion-transmitted sCJD, if any, is likely to be very low.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1537-2995.2011.03459.xDOI Listing
June 2012

Can mortality data provide reliable indicators for Creutzfeldt-Jakob disease surveillance? A study in France from 2000 to 2008.

Neuroepidemiology 2011 2;37(3-4):188-92. Epub 2011 Nov 2.

AP-HP, Cellule Nationale de Référence des Maladies de Creutzfeldt-Jakob, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.

Background: Surveillance of Creutzfeldt-Jakob disease (CJD) is still an important issue because of the variant CJD epidemic, which is in decline and also because of the emergence of novel forms of animal transmissible spongiform encephalopathy with zoonotic potential and the risk of nosocomial and blood transfusion-related transmission. Active surveillance has been implemented in most European countries and requires important human resources and funding. Here, we studied whether national mortality and morbidity statistics can be used as reliable indicators.

Methods: CJD data collected by the French national CJD surveillance centre were compared with data registered in the national mortality statistics.

Results: From 2000 to 2008, the two sources reported fairly similar numbers of CJD deaths. However, analysis of individual data showed important between-sources disagreement. Nearly 24% of CJD reported by the mortality register were false-positive diagnoses and 21.6% of the CJD cases diagnosed by the surveillance centre were not registered as CJD in the national mortality statistics. One out of 22 variant CJD cases was not reported as having any type of CJD in the mortality statistics.

Conclusions: These findings raise doubt about the possibility of a reliable CJD surveillance only based on mortality data.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000332764DOI Listing
March 2012

Abdominal obesity and late-onset asthma: cross-sectional and longitudinal results: the 3C study.

Obesity (Silver Spring) 2012 Mar 20;20(3):628-35. Epub 2011 Oct 20.

INSERM U700, Faculté de Médecine Xavier Bichat, Paris, France.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/oby.2011.308DOI Listing
March 2012

Guillain-Barre syndrome, influenzalike illnesses, and influenza vaccination during seasons with and without circulating A/H1N1 viruses.

Am J Epidemiol 2011 Aug 7;174(3):326-35. Epub 2011 Jun 7.

LA-SER, Paris, France.

The role of influenzalike illnesses and influenza vaccination in the development of Guillain-Barré syndrome (GBS), particularly the role of A/H1N1 epidemics and A/H1N1 vaccination, is debated. Data on all incident GBS cases meeting the Brighton Collaboration criteria that were diagnosed at 25 neurology centers in France were prospectively collected between March 2007 and June 2010, covering 3 influenzavirus seasons, including the 2009-2010 A/H1N1 outbreak. A total of 457 general practitioners provided a registry of patients from which 1,080 controls were matched by age, gender, index date (calendar month), and region to 145 cases. Causal relations were assessed by multivariate case-control analysis with adjustment for risk factors (personal and family history of autoimmune disorders, among others), while matching on age, gender, and calendar time. Influenza (seasonal or A/H1N1) or influenzalike symptoms in the 2 months preceding the index date was associated with GBS, with a matched odds ratio of 2.3 (95% confidence interval (CI): 0.7, 8.2). The difference in the rates of GBS occurring between influenza virus circulation periods and noncirculation periods was highly statistically significant (P = 0.004). Adjusted odds ratios for GBS occurrence within 6 weeks after seasonal and A/H1N1 vaccination were 1.3 (95% CI: 0.4, 4.1) and 0.9 (95% CI: 0.1, 7.6), respectively. Study results confirm that influenza virus is a likely risk factor for GBS. Conversely, no new concerns have arisen regarding influenza vaccination.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/aje/kwr072DOI Listing
August 2011

Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease.

Nat Genet 2011 May 3;43(5):429-35. Epub 2011 Apr 3.

Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Neurosciences and Mental Health Research Institute, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, UK.

We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ≤ 1 × 10(-5). We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10(-17); including ADGC data, meta P = 5.0 × 10(-21)) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10(-14); including ADGC data, meta P = 1.2 × 10(-16)) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10(-4); including ADGC data, meta P = 8.6 × 10(-9)), CD33 (GERAD+, P = 2.2 × 10(-4); including ADGC data, meta P = 1.6 × 10(-9)) and EPHA1 (GERAD+, P = 3.4 × 10(-4); including ADGC data, meta P = 6.0 × 10(-10)).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/ng.803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084173PMC
May 2011

Masked hypertension in the elderly: cross-sectional analysis of a population-based sample.

Am J Hypertens 2011 Jun 17;24(6):674-80. Epub 2011 Mar 17.

INSERM, U708, Paris, France.

Background: Masked hypertension (MHT), defined as normal blood pressure (BP) at office associated with high BP at home, has been shown to be associated with an increased risk of vascular events. However, MHT is poorly known in the elderly, although this age segment is at high risk of hypertension-related vascular events. Our objectives were to assess frequency and determinants of MHT in the elderly.

Methods: We studied MHT in a community-based sample of 1,814 participants aged 75 years or older, whose office BP and home BP measurements (HBPM) were both taken with the same device (Omron M6; Omron Healthcare, Kyoto, Japan).Hypertension was defined as a systolic BP (SBP) ≥ 140 mm Hg and/or a diastolic BP (DBP) ≥ 90 mm Hg for office BP, and SBP ≥ 135 mm Hg and/or DBP ≥ 85 mm Hg for HBPM.

Results: Frequency of MHT was 16% in the overall sample and 41% in participants with a normal office BP. Multivariable analyses revealed that male subjects, >80 years of age, with diabetes, on antihypertensive medication, and with office SBP >120 mm Hg were independently associated with a higher risk of MHT.

Conclusion: MHT is frequent in the elderly and is associated with a high vascular profile. These results should encourage a more widespread use of home BP monitoring in this age segment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/ajh.2011.23DOI Listing
June 2011

Incidence of ischaemic stroke according to income level among older people: the 3C study.

Age Ageing 2011 Jan 10;40(1):116-21. Epub 2010 Nov 10.

EHESP-Epidemiology, Avenue du Pr Léon-Bernard, Rennes 35043, France.

Background: stroke has been shown to follow a social gradient with incidence rising as socioeconomic status decreases.

Objective: to examine the relationship between socioeconomic status and ischaemic stroke risk amongst older people.

Setting: the Cities of Bordeaux, Dijon and Montpellier in France.

Subjects And Methods: nine thousand and two hundred and ninety-four non-institutionalised persons aged 65 years or more followed for 6 years.

Results: the distribution of cardiovascular risks factors was consistent with the classical finding of more favourable risk profiles among the advantaged socioeconomic groups. One hundred and thirty-six individuals developed a first ever ischaemic stroke (incidence rate: 3.2 per 1,000 py (person-years), 95% CI 2.7-3.8). The age- and sex-adjusted incidence of ischaemic stroke increased with increasing level of income (from 2.4 to 4.1 per 1,000 py, P = 0.04). In the multivariable analysis adjusting for cardiovascular risk factors, the higher income group displayed a 80% increased risk of ischaemic stroke compared with less wealthy participants (hazards ratio 1.77, 95% CI 1.20-2.61).

Conclusions: in this community-based sample of older individuals, a higher level of household income was associated with a higher risk of ischaemic stroke, a reversal of the social gradient usually reported in younger age groups. Selective survival is one of the potential explanations for this unexpected finding.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ageing/afq142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3309883PMC
January 2011

The CALHM1 P86L polymorphism is a genetic modifier of age at onset in Alzheimer's disease: a meta-analysis study.

J Alzheimers Dis 2010 ;22(1):247-55

Unité INSERM 744, Institut Pasteur de Lille BP 245,1, rue du professeur Calmette, F59019Lille cedex, France.

The only established genetic determinant of non-Mendelian forms of Alzheimer's disease (AD) is the ε4 allele of the apolipoprotein E gene (APOE). Recently, it has been reported that the P86L polymorphism of the calcium homeostasis modulator 1 gene (CALHM1) is associated with the risk of developing AD. In order to independently assess this association, we performed a meta-analysis of 7,873 AD cases and 13,274 controls of Caucasian origin (from a total of 24 centers in Belgium, Finland, France, Italy, Spain, Sweden, the UK, and the USA). Our results indicate that the CALHM1 P86L polymorphism is likely not a genetic determinant of AD but may modulate age of onset by interacting with the effect of the ε4 allele of the APOE gene.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/JAD-2010-100933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2964875PMC
August 2011

Familial aggregation in atypical Parkinson's disease: a case control study in multiple system atrophy and progressive supranuclear palsy.

J Neurol 2010 Aug 13;257(8):1388-93. Epub 2010 Jul 13.

Intramural Research Program, Laboratory of Epidemiology, Demography and Biometry, National Institute on Aging, National Institutes of Health, 7201 Wisconsin Avenue, Gateway Building, Suite 3C309, Bethesda, MD 20892-9205, USA.

Familial aggregation has been consistently found in PD, but it is unclear whether there is a familial aggregation in families of patients with multiple system atrophy (MSA) or progressive supranuclear palsy (PSP). MSA and PSP cases were recruited from a two-arm case control study. One control was matched to each case for age, gender and living area. Medical history of first-degree relatives was obtained through a face-to-face questionnaire. Age-specific cumulative incidence of Parkinsonism and dementia in first-degree relatives of cases and controls was compared for MSA and PSP separately. Seventy-one pairs for MSA and their controls and 79 pairs for PSP and their controls were included. No significant familial aggregation was found in PSP. MSA cases reported Parkinsonism more often, but not dementia in their first-degree relatives than controls. MSA patients, but not those with PSP, have Parkinsonism more often in their first-degree relatives than controls.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00415-010-5638-9DOI Listing
August 2010

Joint effect of white matter lesions and hippocampal volumes on severity of cognitive decline: the 3C-Dijon MRI study.

J Alzheimers Dis 2010 ;20(2):453-63

Inserm, U708 Neuroepidemiology, Paris, France.

Several brain magnetic resonance imaging (MRI) changes are observed in older individuals including white matter lesions (WML), silent brain infarcts (SBI), and cerebral atrophy. Few studies, however, have assessed the combined association of these changes on the severity of future cognitive decline. In the prospective population-based 3C-Dijon MRI study, 1701 non-demented participants aged 65 to 80 years at entry had a brain MRI. Information on WML, hippocampal volumes, SBI presence, and brain parenchymal fraction were obtained. At 4-year follow-up, participants were screened for cognitive decline and dementia. Severity of cognitive decline was defined as none, moderate, or severe calculated from neuropsychological test performance change. The relation between brain MRI markers and longitudinal change in cognition was studied using polytomous logistic regression and multiple linear regression models controlling for potential confounders. Two-by-two interactions were tested including with the apolipoprotein E genotype. At follow-up, 46 participants showed severe cognitive deterioration and 224 participants showed moderate cognitive deterioration. In multivariable analyses, risk of severe cognitive deterioration as well as the cognitive decline rate were significantly increased in participants with higher WML volume (p< 0.01) and smaller hippocampal volume (p< 0.01). The results suggested that WML and hippocampal volumes had a cumulative effect on the future level of cognitive decline. The APOE genotype was found to be an effect modifier of this association. Vascular brain changes and degenerative processes coexist in normal older individuals. The co-occurrence of degenerative and non-degenerative pathologies could strongly affect the course of dementia expression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/JAD-2010-1389DOI Listing
September 2010

Slow walking speed and cardiovascular death in well functioning older adults: prospective cohort study.

BMJ 2009 Nov 10;339:b4460. Epub 2009 Nov 10.

INSERM, U708, F-75013, Paris, France.

Objective: To study the relation between low walking speed and the risk of death in older people, both overall and with regard to the main causes of death.

Design: Prospective cohort study.

Setting: Dijon centre (France) of the Three-City study.

Participants: 3208 men and women aged >or=65 living in the community, recruited from 1999 to 2001, and followed for an average of 5.1 years.

Main Outcome Measures: Mortality, overall and according to the main causes of death, by thirds of baseline walking speed (measured at maximum speed over six metres), adjusted for several potential confounders; Kaplan-Meier survival curves by thirds of baseline walking speed. Vital status during follow-up. Causes of death. Results During 16 414 person years of follow-up, 209 participants died (99 from cancer, 59 from cardiovascular disease, 51 from other causes). Participants in the lowest third of baseline walking speed had an increased risk of death (hazard ratio 1.44, 95% confidence interval 1.03 to 1.99) compared with the upper thirds. Analyses for specific causes of death showed that participants with low walking speed had about a threefold increased risk of cardiovascular death (2.92, 1.46 to 5.84) compared with participants who walked faster. There was no relation with cancer mortality (1.03, 0.65 to 1.70). In stratified analyses, cardiovascular mortality was increased across various strata defined by sex, median age, median body mass index (BMI), and level of physical activity. Conclusion Slow walking speed in older people is strongly associated with an increased risk of cardiovascular mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2776130PMC
http://dx.doi.org/10.1136/bmj.b4460DOI Listing
November 2009