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.

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.

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.

[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.

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.

[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.

Sustained anxiety and 4-year progression of carotid atherosclerosis.

Several studies have shown that anxiety disorders are associated with a higher risk of coronary artery disease. However, the relationship between anxiety disorders and atherosclerosis has been studied to a lesser extent. The goal of this study was to examine whether high and stable trait anxiety was associated with the progression of atherosclerosis. The study group consisted of 726 subjects (297 men and 429 women), aged 59 to 71 years, recruited from the electoral rolls of the city of Nantes. The subjects had no history of coronary artery disease at baseline evaluation and or at the 2-year follow-up. Two follow-up examinations were conducted 2 and 4 years after the baseline evaluation. Trait anxiety was evaluated by means of the French translation of the Spielberger Inventory (a 20-item trait inventory, form X-2). The "sustained anxiety" group consisted of men and women with the highest Spielberger Inventory scores at baseline and at the 2-year follow-up examination. Each ultrasound examination included measurement of intima-media thickness and the sites of plaque in the extracranial carotid arteries. Men with sustained anxiety showed a higher 4-year increase of common carotid intima-media thickness than did men without sustained anxiety (adjusted means 0.08 versus 0.04 mm, respectively; P=0.05) and a higher risk of 4-year plaque occurrence (adjusted OR 3.5, 95% CI 1.4 to 8.5). Among women, sustained anxiety was associated with a higher 4-year increase of common carotid intima-media thickness (0.07 versus 0.04 for women with versus women without sustained anxiety, respectively; P=0.07). These results suggest that chronically high levels of anxiety may contribute to accelerating the evolution of carotid atherosclerosis.

Predictors of survival in sporadic Creutzfeldt-Jakob disease and other human transmissible spongiform encephalopathies.

A collaborative study of human transmissible spongiform encephalopathies has been carried out from 1993 to 2000 and includes data from 10 national registries, the majority in Western Europe. In this study, we present analyses of predictors of survival in sporadic (n = 2304), iatrogenic (n = 106) and variant Creutzfeldt-Jakob disease (n = 86) and in cases associated with mutations of the prion protein gene (n = 278), including Gerstmann-Sträussler-Scheinker syndrome (n = 24) and fatal familial insomnia (n = 41). Overall survival for each disease type was assessed by the Kaplan-Meier method and the multivariate analyses by the Cox proportional hazards model. In sporadic disease, longer survival was correlated with younger age at onset of illness, female gender, codon 129 heterozygosity, presence of CSF 14-3-3 protein and type 2a prion protein type. The ability to predict survival based on patient covariates is important for diagnosis and counselling, and the characterization of the survival distributions, in the absence of therapy, will be an important starting point for the assessment of potential therapeutic agents in the future.

[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.

[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.

[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.

[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.

[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.

Changes in cognitive abilities over a 4-year period are unfavorably affected in elderly diabetic subjects: results of the Epidemiology of Vascular Aging Study.

OBJECTIVE: To compare 4-year changes in cognitive performance among elderly subjects according to category of fasting blood glucose (FBG) using American Diabetes Association criteria. RESEARCH DESIGN AND METHODS: Subjects without any detectable cognitive dysfunction were selected from the Epidemiology of Vascular Aging (EVA) Study, a cohort of community-dlwelling people aged 59-71 years at baseline. They were classified into glucose categories (normal, impaired fasting glucose [IFG], or diabetic) based on FBG values or known diabetes. Their cognitive abilities were assessed by a global test (Mini Mental Status Examination [MMSE]) and eight domain-specific tests, and they were reassessed 4 years later. Serious cognitive worsening was defined as a score evolution into the worst 15% of the sample's distribution of score differences (4-year score minus baseline score) for each test. RESULTS: At baseline, age-, sex-, and education-adjusted scores for all cognitive tests except one were similar across glucose categories. After 4 years, diabetic subjects had a lower performance on all tests except the MMSE, with differences reaching statistical significance on four tests. Adjusted odds ratios for serious worsening over 4 years in diabetic subjects, with reference to normal subjects, were >2 for four tests (P < 0.05) and bordering this value for two others (P < 0.09). Further adjustment for blood pressure or potential cognition-affecting substances (alcohol, tobacco, and medications) did not modify these results. CONCLUSIONS: Despite similar high initial cognitive function, diabetic subjects tended to have an unfavorable evolution of cognitive performance over 4 years compared with subjects who had normal glucose or IFG.

Effect of the angiotensin I-converting enzyme I/D polymorphism on cognitive decline. The EVA Study Group.

Several clinical, epidemiological, and pathological observations suggest that vascular risk factors are associated with cognitive performances. The renin-angiotensin system components, major determinants of the cardiovascular system, are expressed in the brain. To estimate their potential impact on cognitive performances, we studied the association between cognitive functioning and an insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) gene. In a sample of 1168 highly performing subjects (59-71 years), DD homozygotes had the lowest cognitive scores as evaluated by the Mini-Mental State Examination. Cognitive decline at 4-year follow-up (defined as the loss of at least 3 points in Mini-Mental State Examination score) was more prevalent in these subjects, the odds ratio being equal to 1.53 (95% CI: 1.04-2.24) with subjects ID as reference class. Moreover, the combined effect of the presence of at least one APOE epsilon4 allele and ACE DD homozygosity was a risk factor for cognitive decline. This report reinforces the hypothesis of an influence of cardiovascular risk factors on cognitive performances.

Prediction of long-term outcome in the early hours following acute ischemic stroke. Italian Acute Stroke Study Group.

OBJECTIVE: To develop a model for predicting outcome in the first few hours after the onset of an ischemic stroke on the basis of the clinical findings obtained during a rapid bedside examination. DESIGN: Clinical records were retrieved from the data bank of a randomized multicenter trial. The resulting case series was split into two subgroups that served as a "training set" and a "test set." Logistic regression was applied to the training set to select the prognostic predictors among baseline clinical findings. The performances of the model based on independent prognostic predictors were then validated in the test set. SETTING: Eleven primary care institutions (either hospitals or university clinics) participating in the Italian Acute Stroke Study on the efficacy of hemodilution and monosialoganglioside in acute ischemic stroke. PATIENTS: Consecutive noncomatose patients (N = 300) observed within the first 6 hours after the onset of a first supratentorial ischemic stroke. MAIN OUTCOME MEASURE: Death or disablement 4 months after the index stroke. Disablement was defined as a score of 3 or higher on the Rankin Scale. RESULTS: Age and CNS score defined six risk groups with a predicted 4-month poor outcome rate ranging from 10% (patients aged 70 years or younger and with an initial CNS score of 7 or higher) to 89% (patients older than 70 years and with a CNS score of 4.5 or lower). When a risk of poor outcome of 60% was taken as a cutoff, the accuracy of the prediction was 78% +/- 6% in the training set and 72% +/- 9% in the test set. CONCLUSION: Long-term outcome can be predicted in the first few hours following an acute ischemic stroke by means of a simple model based on age and CNS score.

Increasing trend of ALS in France and elsewhere: are the changes real?

We analyzed 9,005 deaths from amyotrophic lateral sclerosis recorded in France between the years 1968 and 1982. The overall adjusted mortality rates were 1.45/100,000 for men and 0.90/100,000 for women. We found excess male mortality in every age group. Age-specific mortality rates increased with age until 65-74 years and then declined in the older population. There was no meaningful regional pattern. We found a substantial increase in ALS mortality over time: the adjusted rates (per 100,000) in the period 1968 to 1971 were 1.11 for men and 0.63 for women. In the period 1979 to 1982, the corresponding figures were 1.92 and 1.12. The increase was mainly due to persons over 55 years of age and affected mostly the women during the first part of the study (1968 to 1978). In the recent years, increase appeared similar in both sexes. The temporal trends are consistent across studies in different countries.

Cognitive decline in individuals with high blood pressure: a longitudinal study in the elderly. EVA Study Group. Epidemiology of Vascular Aging.

OBJECTIVE: To examine whether baseline high blood pressure and antihypertensive treatment predicts cognitive decline in elderly individuals. METHODS: A longitudinal population-based study of elderly individuals (n = 1,373) in Nantes (western France) was undertaken. Individuals 59 to 71 years of age were selected from electoral rolls. High blood pressure at baseline was defined as systolic blood pressure > or =160 mm Hg or diastolic blood pressure > or =95 mm Hg. Cognitive decline was defined as a drop of 4 points or more on the Mini-Mental State Examination between baseline and the 4-year assessment. RESULTS: There is an association between high blood pressure at baseline and cognitive decline at the 4-year assessment (odds ratio, 2.8; 95% CI, 1.6 to 5.0). In participants with high blood pressure, the risk of cognitive decline was 4.3 (95% CI, 2.1 to 8.8) in those without antihypertensive therapy and 1.9 (95% CI, 0.8 to 4.4) in those being treated. In participants with high blood pressure both at baseline and at the 2-year assessment, the risk for untreated participants was 6.0 (95% CI, 2.4 to 15.0) compared with 1.3 (95% CI, 0.3 to 4.9) in treated participants. CONCLUSIONS: High blood pressure was associated with cognitive decline. In individuals with high blood pressure, cognitive decline occurred in a relatively short time period and the risk was highest in untreated hypertensive patients.