[Ethics of clinical trials]. / L'éthique des essais thérapeutiques.

TITLE: L'éthique des essais thérapeutiques. ABSTRACT: La pandémie de COVID-19 a conduit certains acteurs reconnus de la médecine à renoncer aux méthodes codifiées de la recherche médicale au profit d'affirmations établies dans l'urgence et sans réelle évaluation scientifique. Autant l'on peut comprendre que certains praticiens recourent à ce qui leur est ainsi proposé, autant cette confusion entre action dans l'urgence et recherche scientifique serait lourde de conséquences si elle venait à se généraliser, et cela à de multiples points de vue : image et rôle de la science, qualité et éthique de la recherche médicale et en fin de compte sort des malades soumis à des traitements mal évalués. Ce sont ces questions qui motivent la mise au point qui suit sur les questions d'éthique associées de longue date aux « essais thérapeutiques ¼, cette procédure rationnelle d'acquisition dans les meilleurs délais d'informations fiables sur les avantages et les risques des traitements dont on envisage l'éventuelle utilisation.

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

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 (cm3) 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]; P=0.023) and follow-up (adjusted rate ratio, 3.05 [95% CI, 1.25-7.43]; P=0.014). Lacunes at baseline were also associated with depressed nonusers (adjusted rate ratio, 1.53 [95% CI, 1.06-2.21]; P=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.

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

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.

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

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.

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

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.

Plasma lipids and cerebral small vessel disease.

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 (ß ± SE = 0.0882 ± 0.0302, p = 0.0035), in the EVA Study (ß ± SE = 0.1062 ± 0.0461, p = 0.021), and in the combined analysis (ß ± 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.

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

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.

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

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.

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

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.

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

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.

Intensity of human prion disease surveillance predicts observed disease incidence.

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.

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

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.

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

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%.

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

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.

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.

[Historical cohorts: contribution to epidemiological knowledge]. / Les cohortes historiques: contribution aux progrès de l'épidémiologie.

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.

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

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.

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.