Impact of allopurinol on risk of myocardial infarction.

BACKGROUND: Gout therapy includes xanthine oxidase inhibitors (XOI) and colchicine, which have both been associated with decreased cardiovascular risk. However, their effects on major cardiac events, such as myocardial infarction (MI), need to be investigated further. OBJECTIVES: To investigate whether XOIs and colchicine are associated with decreased risk of MI. METHODS: This case-control study compared patients with first-ever MI and matched controls. Cases were recruited from the Pharmacoepidemiological General Research on MI registry. Controls were selected from a referent population (n=8444) from general practice settings. RESULTS: The study sample consisted of 2277 MI patients and 4849 matched controls. Use of allopurinol was reported by 3.1% of cases and 3.8 of controls, and 1.1% of cases and controls used colchicine. The adjusted OR (95% CI) for MI with allopurinol use was 0.80 (0.59 to 1.09). When using less stringent matching criteria that allowed for inclusion of 2593 cases and 5185 controls, the adjusted OR was 0.73 (0.54 to 0.99). Similar results were found on analysis by sex and hypertension status. Colchicine used was not associated with a decreased risk of MI (aOR=1.17 (0.70 to 1.93)). CONCLUSIONS: Allopurinol may be associated with a reduced risk of MI. No decreased risk of MI was found in colchicine users. Besides its urate-lowering property, allopurinol might have a cardioprotective effect.

A genome-wide association meta-analysis of plasma Aß peptides concentrations in the elderly.

Amyloid beta (Aß) peptides are the major components of senile plaques, one of the main pathological hallmarks of Alzheimer disease (AD). However, Aß peptides' functions are not fully understood and seem to be highly pleiotropic. We hypothesized that plasma Aß peptides concentrations could be a suitable endophenotype for a genome-wide association study (GWAS) designed to (i) identify novel genetic factors involved in amyloid precursor protein metabolism and (ii) highlight relevant Aß-related physiological and pathophysiological processes. Hence, we performed a genome-wide association meta-analysis of four studies totaling 3 528 healthy individuals of European descent and for whom plasma Aß1-40 and Aß1-42 peptides levels had been quantified. Although we did not observe any genome-wide significant locus, we identified 18 suggestive loci (P<1 × 10(-)(5)). Enrichment-pathway analyses revealed canonical pathways mainly involved in neuronal functions, for example, axonal guidance signaling. We also assessed the biological impact of the gene most strongly associated with plasma Aß1-42 levels (cortexin 3, CTXN3) on APP metabolism in vitro and found that the gene protein was able to modulate Aß1-42 secretion. In conclusion, our study results suggest that plasma Aß peptides levels are valid endophenotypes in GWASs and can be used to characterize the metabolism and functions of APP and its metabolites.

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 patient's risk of dementia, especially in those without conditions indicative of potential cognitive impairment.

Risk factors for progressive supranuclear palsy: a case-control study in France.

BACKGROUND: The risk factors of progressive supranuclear palsy (PSP), a rare but severe Parkinsonian syndrome, are poorly known. OBJECTIVE: To study the risk factors of PSP in a case control study among French patients. METHOD: The study was conducted between April 2000 and December 2003. Cases were in- or outpatients of five large hospitals and fulfilled the Golbe criteria. Controls were relatives of patients from the same hospitals, free of Parkinsonian syndrome and dementia, and matched to cases for age, gender and living area. Data on demographic characteristics, occupation history, diet habits, anti-inflammatory drugs use, alcohol consumption, smoking habits, gardening and leisure activities, and exposure to pesticides were collected through a face-to-face questionnaire. A conditional logistic regression was used to analyse matched data and estimate OR. RESULTS: 79 cases and 79 controls were included. Only a few comparisons were significant. Cases reached a lower education attainment than controls (odds ratio (OR) = 2.6 (1.3 to 5.3), p = 0.01). Analysis of diet habits did not show any major difference although cases ate meat or poultry more frequently. Conversely, controls ate fruits more frequently than did cases. No association was found between PSP and occupation, use of pesticides, gardening, alcohol consumption, smoking habits and anti-inflammatory agent use. CONCLUSION: In this case-control study, we did not find any strong environmental risk factors for PSP.

Association of plasma amyloid beta with risk of dementia: the prospective Three-City Study.

OBJECTIVE: Several lines of evidence indicate that a decrease in the CSF concentration of amyloid beta(42) (Abeta(42)) is a potential biomarker for incident Alzheimer disease. In contrast, studies on plasma Abeta(1-40) and Abeta(1-42) peptide levels have yielded contradictory results. Here, we explored the links between incident dementia and plasma Abeta(1-40) and Abeta(1-42) peptide concentrations in the prospective, population-based Three-City (3C) Study. We also assessed the association between plasma concentrations of truncated Abeta (Abeta(n-40) and Abeta(n-42)) and the risk of dementia. METHODS: During a subsequent 4-year follow-up period, 257 individuals presented incident dementia from 8,414 participants, and a subcohort of 1,185 individuals without dementia was drawn as a control cohort. Plasma levels of Abeta(1-40), Abeta(1-42), Abeta(n-40), and Abeta(n-42) were measured using an xMAP-based assay technology. The association between plasma Abeta peptide levels and the risk of dementia was assessed using Cox proportional hazard models. RESULTS: Of the various Abeta variables analyzed, the Abeta(1-42)/Abeta(1-40) and Abeta(n-42)/Abeta(n-40) ratios presented the strongest association with the risk of dementia: people with a high Abeta(1-42)/Abeta(1-40) or Abeta(n-42)/Abeta(n-40) ratio had a lower risk of developing dementia. These associations were restricted to individuals diagnosed at 2 years of follow-up and the Abeta(n-42)/Abeta(n-40) ratio was mainly associated with the risk of mixed/vascular dementia. CONCLUSION: Plasma Abeta peptide concentrations and Abeta(1-42)/Abeta(1-40) and Abeta(n-42)/Abeta(n-40) ratios may be useful markers to indicate individuals susceptible to short-term risk of dementia.

[Epidemiological surveillance of Creutzfeldt-Jakob in France]. / Le réseau de surveillance de la maladie de Creutzfeldt-Jakob.

INTRODUCTION: Transmissible spongiform encephalopathies (TSE) have been under epidemiological surveillance in France and in Europe since the early 1990s. The observation of iatrogenic Creutzfeldt-Jakob disease (CJD), the outbreak of bovine spongiform encephalopathy (ESB) and its probable transmission to many species gave rise to the surveillance which remains warranted by the emergence of a variant of CJD (vCJD), in 1996. STATE OF ART: In France, epidemiological surveillance is coordinated by the InVS which receives input from cases notifications addressed to INSERM Unit 708 directly by clinicians or more often following requests for 14-3-3 detection in CSF. All suspected cases are followed up until a final diagnosis is established. Thanks to the effectiveness of the French network of neuropathology, autopsies are performed in more than half of patients who die with a diagnosis of suspected CJD. Diagnostic criteria allow comparison of the incidence of the different forms of the disease in all countries with a system of surveillance. Sporadic CJD is the most frequent form of the disease with more than 80% of the cases. Its origin remains unknown. To date, cases of iatrogenic CJD referred to the French surveillance network have been caused by dura mater grafts or human growth hormone treatments administrated in the 1980s. Ten percent of TSE are of genetic origin with an autosomic dominant transmission of a mutation or an insertion located on the PRNP gene. The most recent form of the disease is vCJD which is a new form, first described in the United Kingdom in 1994. PROSPECT AND CONCLUSION: Active epidemiological surveillance remains a timely issue, particularly in France, because of the development of new cases of iatrogenic CJD after human growth hormone treatment. It is of importance in France and worldwide because of the emergence of post-transfusional cases of vCJD and the possible appearance of vCJD in persons with valine-valine or methionine-valine genotypes at codon 129.

[Epidemiology, prevention, screening and diagnosis of hepatocellular carcinoma]. / Epidémiologie, prévention, dépistage et diagnostic du carcinome hépatocellulaire.

Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer and occurs mainly in patients with cirrhosis. This work aimed at reviewing the main data and trends about HCC epidemiology in France, and about prevention, screening and diagnosis in patients with chronic liver diseases. The six following research topics were considered as priorities: 1) to improve epidemiological knowledge of HCC in France; 2) to clarify the epidemiology of HCC occuring in normal liver and to identify predictive factors; 3) to prevent cancer occurrence in patients with cirrhosis; 4) to improve the knowledge of predictive factors for HCC occurrence in patients with cirrhosis; 5) to improve the diagnostic procedure of nodules below 2 cm in diameter in patients with cirrhosis; 6) to understand functioning of medical networks in order to identify the reasons for late diagnosis and treatment of HCC in patients with cirrhosis.

Transcriptomic and genetic studies identify IL-33 as a candidate gene for Alzheimer's disease.

The only recognized genetic determinant of the common forms of Alzheimer's disease (AD) is the epsilon 4 allele of the apolipoprotein E gene (APOE). To identify new candidate genes, we recently performed transcriptomic analysis of 2741 genes in chromosomal regions of interest using brain tissue of AD cases and controls. From 82 differentially expressed genes, 1156 polymorphisms were genotyped in two independent discovery subsamples (n=945). Seventeen genes exhibited at least one polymorphism associated with AD risk, and following correction for multiple testing, we retained the interleukin (IL)-33 gene. We first confirmed that the IL-33 expression was decreased in the brain of AD cases compared with that of controls. Further genetic analysis led us to select three polymorphisms within this gene, which we analyzed in three independent case-control studies. These polymorphisms and a resulting protective haplotype were systematically associated with AD risk in non-APOE epsilon 4 carriers. Using a large prospective study, these associations were also detected when analyzing the prevalent and incident AD cases together or the incident AD cases alone. These polymorphisms were also associated with less cerebral amyloid angiopathy (CAA) in the brain of non-APOE epsilon 4 AD cases. Immunohistochemistry experiments finally indicated that the IL-33 expression was consistently restricted to vascular capillaries in the brain. Moreover, IL-33 overexpression in cellular models led to a specific decrease in secretion of the A beta(40) peptides, the main CAA component. In conclusion, our data suggest that genetic variants in IL-33 gene may be associated with a decrease in AD risk potentially in modulating CAA formation.

Dietary patterns and risk of dementia: the Three-City cohort study.

BACKGROUND: Dietary fatty acids and antioxidants may contribute to decrease dementia risk, but epidemiologic data remain controversial. The aim of our study was to analyze the relationship between dietary patterns and risk of dementia or Alzheimer disease (AD), adjusting for sociodemographic and vascular risk factors, and taking into account the ApoE genotype. METHODS: A total of 8,085 nondemented participants aged 65 and over were included in the Three-City cohort study in Bordeaux, Dijon, and Montpellier (France) in 1999-2000 and had at least one re-examination over 4 years (rate of follow-up 89.1%). An independent committee of neurologists validated 281 incident cases of dementia (including 183 AD). RESULTS: Daily consumption of fruits and vegetables was associated with a decreased risk of all cause dementia (hazard ratio [HR] 0.72, 95% CI 0.53 to 0.97) in fully adjusted models. Weekly consumption of fish was associated with a reduced risk of AD (HR 0.65, 95% CI 0.43 to 0.994) and all cause dementia but only among ApoE epsilon 4 noncarriers (HR 0.60, 95% CI 0.40 to 0.90). Regular use of omega-3 rich oils was associated with a decreased risk of borderline significance for all cause dementia (HR 0.46, 95% CI 0.19 to 1.11). Regular consumption of omega-6 rich oils not compensated by consumption of omega-3 rich oils or fish was associated with an increased risk of dementia (HR 2.12, 95% CI 1.30 to 3.46) among ApoE epsilon 4 noncarriers. CONCLUSION: Frequent consumption of fruits and vegetables, fish, and omega-3 rich oils may decrease the risk of dementia and Alzheimer disease, especially among ApoE epsilon 4 noncarriers.

[vCJD epidemiology in France]. / Epidémiologie de la variante de la maladie de Creutzfeldt-Jakob en France.

Variant Creutzfeldt-Jakob disease (vCJD) is the only form of prion diseases linked to bovine spongiform encephalopathy (BSE). The disease was first described in the United-Kingdom (UK) and France is the second affected country with 21 cases. Clinical, genetic and neuropathological features are the same in both countries. Comparison of the total number of cases in France and in the UK, according to dates of onset, shows that, in France, the maximum incidence seems to be five years delayed and that, in the UK, the number of vCJD cases regularly decreases since 1999. Delayed exposure to contaminated beef products in France compared to the UK could explain this temporal gap. Three cases of vCJD after transfusion of labile blood products were observed in the UK. No such of cases were observed in France but three patients developing signs of vCJD in 2004 were blood donors. A total of 42 recipients were identified with 17 recipients still alive.

Cross-sectional association between homocysteine and motor function in the elderly.

OBJECTIVE: To determine if there is a cross-sectional association between homocysteine (tHcy) level and measures of gait and balance in elderly subjects. METHODS: We studied 3,609 noninstitutionalized subjects aged 65 to 85 years from the Dijon (France) center of the Three-City Study. tHcy concentration was measured from fasting blood samples. Motor function was assessed by measuring walking speed and by using a modified version of the Tinetti scale. RESULTS: After adjustment for confounders, mean maximum walking speed (MWS) decreased with increasing tHcy levels (p = 0.001). The odds ratio (OR) (95% CI) for having a MWS below the 40th percentile was 1.9 (1.4 to 2.5) in subjects with tHcy levels in the upper quintile compared with those in the lowest quintile. Compared with subjects in the lowest tHcy quintile, the OR for having a modified Tinetti score below 16 ranged from 1.0 (0.8 to 1.4) in the second quintile to 1.9 (1.3 to 2.6) in the upper quintile (p < 0.0001). CONCLUSIONS: Elevated homocysteine concentrations are associated with worse motor performances in the elderly. These findings support the hypothesis of a vascular contribution to motor function.

Determinants of diagnostic investigation sensitivities across the clinical spectrum of sporadic Creutzfeldt-Jakob disease.

To validate the provisional findings of a number of smaller studies and explore additional determinants of characteristic diagnostic investigation results across the entire clinical spectrum of sporadic Creutzfeldt-Jakob disease (CJD), an international collaborative study was undertaken comprising 2451 pathologically confirmed (definite) patients. We assessed the influence of age at disease onset, illness duration, prion protein gene (PRNP) codon 129 polymorphism (either methionine or valine) and molecular sub-type on the diagnostic sensitivity of EEG, cerebral MRI and the CSF 14-3-3 immunoassay. For EEG and CSF 14-3-3 protein detection, we also assessed the influence of the time point in a patient's illness at which the investigation was performed on the likelihood of a typical or positive result. Analysis included a large subset of patients (n = 743) in whom molecular sub-typing had been performed using a combination of the PRNP codon 129 polymorphism and the form of protease resistant prion protein [type 1 or 2 according to Parchi et al. (Parchi P, Giese A, Capellari S, Brown P, Schulz-Schaeffer W, Windl O, Zerr I, Budka H, Kopp N, Piccardo P, Poser S, Rojiani A, Streichemberger N, Julien J, Vital C, Ghetti B, Gambetti P, Kretzschmar H. Classification of sporadic Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects. Ann Neurol 1999; 46: 224-233.)] present in the brain. Findings for the whole group paralleled the subset with molecular sub-typing data available, showing that age at disease onset and disease duration were independent determinants of typical changes on EEG, while illness duration significantly influenced positive CSF 14-3-3 protein detection; changes on brain MRI were not influenced by either of these clinical parameters, but overall, imaging data were less complete and consequently conclusions are more tentative. In addition to age at disease onset and illness duration, molecular sub-type was re-affirmed as an important independent determinant of investigation results. In multivariate analyses that included molecular sub-type, time point of the investigation during a patient's illness was found not to influence the occurrence of a typical or positive EEG or CSF 14-3-3 protein result. A typical EEG was most often seen in MM1 patients and was significantly less likely in the MV1, MV2 and VV2 sub-types, whereas VV2 patients had an increased likelihood of a typical brain MRI. Overall, the CSF 14-3-3 immunoassay was the most frequently positive investigation (88.1%) but performed significantly less well in the very uncommon MV2 and MM2 sub-types. Our findings confirm a number of determinants of principal investigation results in sporadic CJD and underscore the importance of recognizing these pre-test limitations before accepting the diagnosis excluded or confirmed. Combinations of investigations offer the best chance of detection, especially for the less common molecular sub-types such as MV2 and MM2.

[Validity of the five-word screening test for Alzheimer's disease in a population based study]. / Le test des 5 mots: validité dans la détection de la maladie d'Alzheimer dans la population générale.

INTRODUCTION: In general medicine lack of time impairs screening for Alzheimer's disease (AD). The five word test (FWT) enables rapid assessment of verbal episodic memory in accordance with Grober and Buschke neuropsychological concept. The main steps of the FWT are: induce specific semantic processing, control of encoding to avoid attention deficits, free and cued recall. Cued recall helps to distinguish a recall impairment from storage impairment which is evocative of AD. OBJECTIVE: Evaluate FWT total score (sum of free and cued recalls), FWT total weighed score which give a higher coefficient for free recalls than cued recalls and present the ability of these two scores for AD screening. METHOD: Evaluation performed with 4116 subjects (of whom 73 MA) aged from 65 years and more, randomly selected in two French towns for the "Three Cities" Study, a population-based cohort. RESULTS: The total score was more specific than sensitive with a maximal sensitivity (Se) at 63 percent with specificity (Sp) at 91.1 percent. The total weighed score significantly increased Se (83.6 percent) with control of specificity (84.9 percent) and positive predictive value (9.1 percent). CONCLUSION: The FWT allows quick screening of patients for whom further neuropsychological evaluation is needed to diagnose AD. The ability of is simple test to screen for AD is improved by a simple weighting procedure: the total weighted score.

[Prevalence of asymptomatic atherothrombotic lesions and risk of vascular events in patients with a stroke]. / Prévalence des lesions athérothrombotiques asymptomatiques et risque d'evénements vasculaires chez un patient ayant eu un accident vasculaire cérébral.

OBJECTIVE: To estimate the prevalence of asymptomatic atherothrombotic lesions and the absolute risk of vascular events in patients with ischemic stroke. METHODS: We conducted a systematic review of studies published between 1980 and 2004 which allowed calculating prevalence of asymptomatic lesions and absolute risks of vascular events in stroke patients. Studies included in the review of absolute risks had to include at least 100 patients followed for at least 1 year and with less than 5% of lost to follow-up. RESULTS: Coronarography was used in only one study which does not provide any precise estimation of the prevalence of asymptomatic coronary lesions. Depending on the population and the method used for the diagnosis of coronary disease, the prevalence of asymptomatic coronary artery disease ranged from 25 through 60%. Very few studies have been devoted to the prevalence of abdominal aortic disease in stroke patients. The prevalence of abdominal aortic aneurysm has been estimated to 1% and that of peripheral arterial disease to 10%. Thirty-six cohorts were identified. The absolute risk of myocardial infarction was about 2%/year and that of vascular death 2%/year. CONCLUSION: Stroke patients carry a high risk of coronary and vascular events. Additional studies are required to better identify patients with a high prevalence of asymptomatic atherosclerotic lesions and with a high risk of vascular events.

[Prevalence of asymptomatic atherothrombotic lesions and risk of vascular events in patients with documented coronary artery disease]. / Prévalence des lésions athérothrombotiques asymptomatiques et risques d'evénements vasculaires chez des patients ayant une maladie coronaire documentée.

Coronary arteries are the most frequent location of atherosclerosis. Coronary artery disease is the first cause of death related to atherothrombosis. In addition, patients with a prior history of acute coronary syndromes exhibit a 10% annual risk of recurrence. Although there seems to be a close correlation between the extension of CAD and the severity of atherosclerotic lesions in extra coronary arterial beds, the prevalence of these extracoronary asymptomatic lesions depends on their location. Hence, the prevalence of renal artery disease defined as stenosis > or = 50% or of peripheral artery disease defined as an ABI < 0.9 is estimated to be 20% up to 30%, whereas the prevalence of both carotid artery disease defined as stenosis > or = 70% or aortic aneurysm is estimated to be 5%. Conversely, the annual absolute risk of stroke among CAD patients is estimated at 1% while it remains unknown for vascular events related to PAD or aortic lesions. These data suggest that a systematic screening for asymptomatic extracoronary atherosclerotic lesions among CAD patients cannot be justified without a better knowledge of the prevalence of these lesions. In addition, the identification of the predicting factors for the presence and the development of these asymptomatic lesions is warranted. Finally, the potential benefit in terms of therapeutic intervention of such screening needs to be evaluated. These important issues warrant further clinical studies with appropriate design.

[Screening strategies for the diagnosis of asymptomatic arterial lesions in patients with atherothrombosis]. / Méthodes de dépistage des localisations artérielles asymptomatiques chez le patient athérothrombotique.

Atherosclerosis is a ubiquitous inflammatory disease. Patients presenting an acute atherothrombotic event (acute coronary syndrom, stroke, aortic aneurysm, ...) have an increased risk of events in remote arterial territories affected by atherosclerosis. These patients could benefit from systematic screening of asymptomatic atherosclerotic lesions to avoid these complications. For each atherosclerotic territory (coronary artery, carotid artery, aorta, peripheral arteries including renal arteries), we review the methods for screening asymptomatic atherothrombotic lesions which could justify specific treatments: coronary artery stenosis > or = 50%, carotid artery stenosis > or = 60%, renal artery stenosis > or = 50%, and abdominal aortic aneurysm > or = 30 mm. This review shows that non invasive methods (ie, echography, tomodensitometry) are widely available for diagnosis of asymptomatic lesions in carotid and renal arteries, and in the aorta. Despite its invasive caracteristic, coronarory angiography remains the gold-standard for the diagnosis of coronary artery disease. However, cardiac multi-slices CT-scan appears a promising technique for asymptomatic patients.

[Epidemiology of athrotherombotic lower limb arterial disease]. / Epidémiologie de l'artériopathie des membres inférieurs d'origine athérothrombotique.

Chronic occlusive arterial disease of the lower limbs is a common presentation of atherothrombotic disease. This systematic review of the literature analyses the natural history of this condition and the prevalence of asymptomatic lesions of other arterial localisations requiring specific treatment. The Medline database was researched and completed by a bibliography of the principal articles selected, Internet sites and their publication reviews and also the Cochrane database. The incidence of systemic complications has been assessed in many good quality epidemiological study. It increases with the severity of lower limb arterial disease, but in asymptomatic patients defined by a pathological systolic pressure index (< 0.90) the cardiovascular mortality is already 2% per year, the incidence of myocardial infarction 3% per year and that of cerebrovascular accidents 1 to 2% per year. The prevalence of asymptomatic lesions in other arterial sites is less well documented, the evaluations varying according to the population studied and criteria of significant lesions: 21 to 69% for coronary artery disease, 12 to 59% for carotid artery stenosis, 14 to 40% for renal artery stenosis and 6 to 14% for abdominal aortic aneurysms. Despite the uncertainty of these estimations, the prevalence of asymptomatic atherothrombotic lesions is high in all arterial networks and justifies the setting up of studies to assess the clinical benefits of their systematic diagnostic investigations.

[Variant Creutzfeldt-Jakob disease in France: estimating the number of cases related to travel to the United Kingdom between 1980 and 1995]. / Le nouveau variant de la maladie de Creutzfeldt-Jakob en France: estimation du nombre de cas attribuables à un séjour dans les îles britanniques entre 1980 et 1995.

BACKGROUND: The outbreak of variant Creutzfeldt-Jakob disease (vCJD) cases rose serious concerns about secondary transmission of the disease, particularly through blood transfusion. Protective measures leading to the exclusion of potentially infectious blood donors were settled: in France, donors who had stayed more than one year in the UK were excluded. In this work, which was part of a larger study aiming to estimate the French epidemic of vCJD, the number of vCJD cases who were infected during a trip to the UK was estimated. Those estimates may notably enable the assessment of such exclusion measures. METHODS: The particular age-related structure in vCJD cases is taken into account in our simulations considering birth cohorts in the population. The total French exposure is simulated assuming the main source of infection to be dietary through consumption of mechanically recovered meat (MRM) manufactured from British bovine carcasses. Then, using a "back calculation" algorithm, all infected individuals required to produce a consistent epidemic (6 vCJD cases in 2003) was simulated. This study was exclusively focused on the part of the exposure linked to trips (beef MRM consumed in the UK while traveling) and on cases resulting from this exposure. RESULTS: The influence of exposure linked to trips to the UK was greater in the youngest cohort (6.3% of the total exposure) while it only accounted for 3.3% and 1% in the 1939-69 and in the pre-1939 birth cohorts respectively. Overall, exposure resulting from trips in the UK can be neglected with regards to the exposure linked to the consumption of MRM produced in France from British bovine carcasses. Consequently, French vCJD cases that would have been infected in the UK are very unlikely to occur (median: 0 case, IC 95%: (0-2)). Nevertheless, if such cases occur, they would probably occur in subjects born after 1969 and their onset would take place before 2010. Thus, unlike the situation in BSE-free countries, the causal relationship between travel in the UK and occurrence of vCJD cases cannot be underlined in France, as trips only account for a small part of the French exposure. CONCLUSION: Since trips in the UK slightly contribute to the overall French exposure, excluding people who travelled in the UK from blood donation would not influence the risk of secondary transmission.

APOE genotype, cholesterol level, lipid-lowering treatment, and dementia: the Three-City Study.

OBJECTIVE: To examine the association of plasma cholesterol levels, lipid-lowering agent (LLA) intake, and APOE genotype with dementia prevalence. METHODS: The Three-City Study is a population-based cohort of 9,294 subjects selected from the electoral rolls of three French cities (Bordeaux, Dijon, Montpellier). Baseline examination included extensive assessment of exposure to vascular risk factors (including cholesterol levels and LLA use [statin or fibrate]) and clinical diagnosis of dementia. RESULTS: Two percent of participants were demented at baseline. Overall 32.4% of participants had hyperlipidemia, and 15.6% were prescribed statins and 13.7% fibrates. After adjusting for age, gender, education level, and study center, the odds ratio (OR) for dementia was observed to be lower among LLA users (OR = 0.61, 95% CI = 0.41 to 0.91) compared with subjects taking no LLAs. There was no differential effect between statin and fibrate users. The odds for dementia were increased in subjects with hyperlipidemia (OR = 1.43, 95% CI = 1.03 to 1.99). Further adjustment for potential confounders did not modify these associations. In addition, the association between LLA intake and dementia was not modified by APOE genotype, whereas hyperlipidemia was significantly associated with increased dementia prevalence only in non-epsilon4 carriers and non-Alzheimer disease cases. Finally, in participants taking LLAs, the odds for dementia were decreased only in those having normal lipid levels. CONCLUSIONS: This observational study provides further evidence that lipid-lowering agents are associated with decreased risk of dementia, whereas hyperlipidemia is associated with increased odds for non-Alzheimer-disease-type dementia. These effects appear to be independent of all major potential confounders.

Mortality from Creutzfeldt-Jakob disease and related disorders in Europe, Australia, and Canada.

BACKGROUND: An international study of the epidemiologic characteristics of Creutzfeldt-Jakob disease (CJD) was established in 1993 and included national registries in France, Germany, Italy, the Netherlands, Slovakia, and the United Kingdom. In 1997, the study was extended to Australia, Austria, Canada, Spain, and Switzerland. METHODS: Data were pooled from all participating countries for the years 1993 to 2002 and included deaths from definite or probable CJD of all etiologic subtypes. RESULTS: Four thousand four hundred forty-one cases were available for analysis and included 3,720 cases of sporadic CJD, 455 genetic cases, 138 iatrogenic cases, and 128 variant cases. The overall annual mortality rate between 1999 and 2002 was 1.67 per million for all cases and 1.39 per million for sporadic CJD. Mortality rates were similar in all countries. There was heterogeneity in the distribution of cases by etiologic subtype with an excess of genetic cases in Italy and Slovakia, of iatrogenic cases in France and the UK, and of variant CJD in the UK. CONCLUSIONS: This study has established overall epidemiologic characteristics for Creutzfeldt-Jakob disease (CJD) of all types in a multinational population-based study. Intercountry comparisons did not suggest any relative change in the characteristics of sporadic CJD in the United Kingdom, and the evidence in this study does not suggest the occurrence of a novel form of human bovine spongiform encephalopathy infection other than variant CJD. However, this remains a possibility, and countries currently unaffected by variant CJD may yet have cases.