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Objectives: In patients with gout, maintaining too low serum uric acid (SUA) level with urate-lowering therapy is a concern because uric acid is thought to be neuroprotective. However, the relation between SUA and dementia remains debated. This study aimed to investigate the impact of SUA level on the incidence of dementia.Methods: We assessed the longitudinal association between SUA level and incident dementia (Diagnostic and Statistical Manual of Mental Disorders Version IV (DSM-IV) criteria) in a large cohort of healthy older people from the community (Three-City Dijon cohort). Additionally, we investigated the relation between SUA level and MRI markers of brain ageing (white matter hyperintensity volume (WMHV), lacunes and hippocampal volume).Results: The study sample comprised 1598 people (mean (SD) age 72.4(4.1) years, 38.3% male). During the 13,357 person-years of follow-up (median duration: 10.1 years), dementia developed in 110 participants (crude incidence rate: 8.2/1000 person-years). After multiple adjustments, the multivariate HR with the highest (≥75th percentile) versus lowest SUA level was 1.79 (95% CI 1.17 to 2.73; p=0.007). The association was stronger with vascular or mixed dementia (HR=3.66 (95% CI 1.29 to 10.41), p=0.015) than Alzheimer's disease (HR=1.55 (95% CI 0.92 to 2.61), p=0.10). There was a non-significant trend towards an association between high SUA level and extensive WMHV (p=0.10), a biomarker of small vessel disease, but not hippocampal volume (p=0.94) or lacunes (p=0.86). The association between SUA level and vascular or mixed dementia might be affected by interim strokes.Conclusions: Risk of dementia, especially vascular or mixed dementia, may be increased with high SUA levels in elderly people. [ABSTRACT FROM AUTHOR]

France is a country of more than 60 million inhabitants, where indicators of health quality are favourable, with one of the longest life expectancies in the world, and one of the lowest rates of neonatal mortality. The burden of vascular diseases is smaller than in surrounding European countries of similar size (United Kingdom and Germany), even for stroke. However, the direct cost of health care provided to stroke patients is estimated between 2 and 2·5 billion Euros per year. [ABSTRACT FROM AUTHOR]

The article discusses a population-based cohort study which investigated the association between use of lipid lowering drugs in older people with no known history of vascular events and long term risk of coronary heart disease and stroke. Topics covered include the study's participants and setting and the design, size and duration of the research. The study's main results are also described.

Introduction: Evaluating whether genetic susceptibility modifies the impact of lifestyle-related factors on dementia is critical for prevention., Methods: We studied 5170 participants from a French cohort of older persons free of dementia at baseline and followed for up to 17 years. The LIfestyle for BRAin health risk score (LIBRA) including 12 modifiable factors was constructed at baseline (higher score indicating greater risk) and was related to both subsequent cognitive decline and dementia incidence, according to genetic susceptibility to dementia (reflected by the apolipoprotein E [APOE] ε4 allele and a genetic risk score [GRS])., Results: The LIBRA was associated with higher dementia incidence, with no significant effect modification by genetics (hazard ratio for one point score = 1.09 [95% confidence interval, 1.05; 1.13]) in APOE ε4 non-carriers and = 1.15 [1.08; 1.22] in carriers; P = 0.15 for interaction). Similar findings were obtained with the GRS and with cognitive decline., Discussion: Lifestyle-based prevention may be effective whatever the genetic susceptibility to dementia., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

This study aims at assessing the burden of rare (minor allele frequency < 1%) predicted damaging variants in the whole exome of 92 bipolar I disorder (BD) patients and 1051 controls of French ancestry. Patients exhibiting an extreme phenotype (earlier onset and family history of mood disorder) were preferentially included to increase the power to detect an association. A collapsing strategy was used to test the overall burden of rare variants in cases versus controls at the gene level. Only protein-truncating and predicted damaging missense variants were included in the analysis. Thirteen genes exhibited p values exceeding 10 -3 and could be considered as potential risk factors for BD. Furthermore, the validity of the association was supported when the Exome Aggregation Consortium database non-Finnish European population was used as controls for eight of them. Their gene products are involved in various cerebral processes, some of which were previously implicated in BD and belong to pathways implicated in the therapeutic effect of lithium, the main mood stabilizer. However, exome-wide threshold for association study was not reached, emphasizing that larger samples are needed.

Background Steroid-sensitive nephrotic syndrome (SSNS) is a childhood disease with unclear pathophysiology and genetic architecture. We investigated the genomic basis of SSNS in children recruited in Europe and the biopsy-based North American NEPTUNE cohort. Methods We performed three ancestry-matched, genome-wide association studies (GWAS) in 273 children with NS (Children Cohort Nephrosis and Virus [NEPHROVIR] cohort: 132 European, 56 African, and 85 Maghrebian) followed by independent replication in 112 European children, transethnic meta-analysis, and conditional analysis. GWAS alleles were used to perform glomerular cis -expression quantitative trait loci studies in 39 children in the NEPTUNE cohort and epidemiologic studies in GWAS and NEPTUNE (97 children) cohorts. Results Transethnic meta-analysis identified one SSNS-associated single-nucleotide polymorphism (SNP) rs1063348 in the 3' untranslated region of HLA-DQB1 ( P =9.3×10 -23 ). Conditional analysis identified two additional independent risk alleles upstream of HLA-DRB1 (rs28366266, P =3.7×10 -11 ) and in the 3' untranslated region of BTNL2 (rs9348883, P =9.4×10 -7 ) within introns of HCG23 and LOC101929163 These three risk alleles were independent of the risk haplotype DRB1*07:01-DQA1*02:01-DQB1*02:02 identified in European patients. Increased burden of risk alleles across independent loci was associated with higher odds of SSNS. Increased burden of risk alleles across independent loci was associated with higher odds of SSNS, with younger age of onset across all cohorts, and with increased odds of complete remission across histologies in NEPTUNE children. rs1063348 associated with decreased glomerular expression of HLA-DRB1, HLA-DRB5, and HLA-DQB1. Conclusions Transethnic GWAS empowered discovery of three independent risk SNPs for pediatric SSNS. Characterization of these SNPs provide an entry for understanding immune dysregulation in NS and introducing a genomically defined classification., (Copyright © 2018 by the American Society of Nephrology.)

Background: Vascular risk factors have been proposed as important targets for the prevention of dementia. As lipid fractions represent easily modifiable targets, we examined the longitudinal relationship of baseline lipid fractions with 13-y incident dementia and its subtypes (Alzheimer disease [AD] and mixed or vascular dementia) in older community-dwelling persons., Methods and Findings: Non-institutionalized persons aged 65+ y (n = 9,294) were recruited for the Three-City Study (3C Study), a population-based cohort study from the electoral rolls of the cities of Dijon, Bordeaux, and Montpellier, France, between March 1999 and March 2001. Follow-up examinations were performed every 2 y after the baseline assessment. The final study sample comprised 7,470 participants from the 3C Study (mean age ± standard deviation [SD] 73.8 ± 5.3 y, 61.0% women) who were prospectively followed up for up to 13 y. Fasting lipid fractions (triglycerides [TGs], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], total cholesterol [TC]) were studied as continuous variables, and results are reported per SD increase of each lipid fraction. Incident dementia and its subtypes were studied as censored variables using Cox models with age as time scale. Analyses were adjusted for sex, study center, and educational level, as well as vascular risk factors and apolipoprotein E (APOE) ε4 genotype. We corrected for multiple testing, yielding a significance threshold of 0.0169. p-Values above the significance threshold but less than 0.05 were considered nominally significant. During a mean (± SD) follow-up period of 7.9 ± 3.6 y, 779 participants developed incident dementia (n = 532 AD and n = 154 mixed or vascular dementia). Higher LDL-C and TC concentrations at baseline were associated with an increased risk of AD (hazard ratio [HR] per SD increase = 1.13 [95% CI 1.04-1.22], p = 0.0045, and HR = 1.12 [1.03-1.22], p = 0.0072, respectively). These associations were largely unchanged after adjustment for vascular risk factors and were attenuated after adjustment for APOEε4 (HR per SD increase = 1.12 [1.03-1.23], p = 0.0110, and HR = 1.12 [1.02-1.23], p = 0.0171, respectively). Higher TG concentrations at baseline were associated with an increased risk of all dementia (HR per SD increase = 1.11 [1.03-1.19], p = 0.0044) and mixed or vascular dementia (HR = 1.21 [1.04-1.41], p = 0.0163). However, these associations disappeared after adjusting for vascular risk factors (HR = 1.07 [0.98-1.17], p = 0.1374, and HR = 1.17 [0.96-1.42], p = 0.1206, respectively). Main limitations of the study include interval censoring of incident dementia cases, potential selective survival bias, and the fact that variation in lipid concentrations during follow-up could not be accounted for in the analyses., Conclusions: In a large population-based sample of older community-dwelling persons with up to 13 y of follow-up, we observed that higher LDL-C and TC concentrations were associated with an increased risk of AD. This result was independent of vascular risk factors and was attenuated after adjustment for APOEε4 carrier status. TG and HDL-C concentrations were not associated with risk of incident dementia or its subtypes after accounting for vascular risk factors.

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., (© Alpérovitch et al 2015.)

Objective: We investigated the relation of circulating plasma β-amyloid (Aβ) with MRI markers of small vessel disease (SVD) in dementia-free community persons., Methods: Participants were 1,690 individuals aged 65 to 80 years from the Three-City Dijon Study. Plasma Aβ measurement and MRI examination were performed at baseline and after a 4-year follow-up. MRI markers of SVD included white matter hyperintensities (WMH), lacunes, and enlarged perivascular spaces. We examined the relation of plasma Aβ levels with MRI markers of SVD at baseline and with progression of WMH over follow-up (n = 1,057). We also assessed whether these relations were modified by vascular risk factors, notably blood pressure., Results: Low plasma Aβ1-40 levels were associated with increased progression of WMH, and low Aβ1-42 with higher odds of extensive WMH progression over the follow-up (odds ratio = 1.66, 95% confidence interval = 1.16-2.38). Consistently low Aβ1-40 and Aβ1-42 levels on both measurements were associated with accelerated progression of WMH. These associations were modified by blood pressure levels but not the APOE ε4 genotype., Conclusions: Progression of WMH volume in dementia-free older persons is associated with levels of circulating plasma Aβ. These results reinforce the notion of an interrelation of vascular and neurodegenerative mechanisms in cerebral aging., (© 2014 American Academy of Neurology.)

Background: Reliable epidemiological data on the true incidence of cerebrovascular events related to spontaneous cervical artery dissection, including stroke and transient ischemic attack, are scarce., Aims: To evaluate the incidence, characteristics, and outcome of cerebrovascular events due to cervical artery dissection., Methods: All cerebrovascular events (stroke and transient ischemic attack) occurring in Dijon, France, from 2006 to 2011, were retrieved from a population-based registry. Patients with a cervical artery dissection were identified. Incidence rates, baseline characteristics, and outcome at three-months were described., Results: Among the 1368 patients with cerebrovascular events, 27 had cervical artery dissection (2·0%, 52% men, mean age 49·1±17·1), including 10 patients with internal carotid artery dissection, 16 patients with vertebral artery dissection, and one patients with both internal carotid artery dissection and vertebral artery dissection. The crude incidence rate of cerebrovascular events due to cervical artery dissection was 2·97/100,000/year. Corresponding rates were 1·21/100,000/year for internal carotid artery dissection, and 1·87/100,000/year for vertebral artery dissection. Seventy per cent of patients had a stroke and among these, higher severity was observed in those with internal carotid artery dissection. A good outcome (m-Rankin score 0-2) was observed in 89% of patients at three-months, whatever the location of the cervical artery dissection. One patient with vertebral artery dissection died at day 38., Conclusion: The incidence of cerebrovascular events related to vertebral artery dissection is greater than previously reported, which may indicate a better identification of patients due to improvements in diagnostic procedures., (© 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.)

Background: Stroke outcomes are worse in patients admitted at nonworking hours (NWH), but whether this is also true in patients treated with intravenous (i.v.) thrombolysis has not been definitely proven., Objective: Our aim was to test the hypothesis that stroke patients treated by i.v. rt-PA at NWH have a worse outcome than those treated at working hours (WH)., Methods: We compared outcomes at 7 days and at 3 months, between patients treated at NWH and at WH in the stroke unit of the Lille University Hospital., Results: Of 252 consecutive patients [median age: 69 years; 132 men (52.4%); median National Institutes of Health Stroke Scale score: 14; median onset-to-needle time: 150 min], 134 (53.2%) were treated at NWH. They did not differ for baseline characteristics and proportion of patients with modified Rankin Scale scores 0-1 and 0-2 at 3 months. Patients treated at WH were more likely to die before 7 days (12.7 vs. 4.5%; adjusted odds ratio: 3.6; 95% confidence interval: 1.2-10.4) and at 3 months (21.6 vs. 11.4%; adjusted odds ratio: 2.2; 95% confidence interval: 1.02-4.7). The causes of death did not differ between NWH and WH. At NWH, there was no difference in baseline characteristics and outcomes of patients treated by stroke- and nonstroke neurologists., Conclusion: The case fatality rates were unexpectedly higher at WH than at NWH. If this finding can be reproduced and is not a chance finding, we should identify explanations, especially organisational issues, chronobiological factors or summation of subtle--nonsignificant--baseline differences., (Copyright (c) 2010 S. Karger AG, Basel.)

Cognitive impairment has seldom been investigated in patients with chronic heart failure (CHF). The authors' aim was to assess the prevalence and determinants of cognitive impairment in patients hospitalized for CHF decompensation. The authors prospectively performed the Folstein Mini-Mental State Examination (MMSE) and completed a standardized questionnaire for cerebrovascular accidents (CVA) and transient ischemic attacks (TIA) in patients hospitalized for CHF decompensation during a 3-month period. A total of 83 patients were studied: 15 had a history of CVA or TIA, 51 (61%) had an MMSE score < or = 28 (or < or = 26 if schooling < or = 8 years), and 26 (31%) had an MMSE score <24. Factors associated with an MMSE score <24 were atrial fibrillation/flutter (odds ratio [OR], 8.1; 95% confidence interval [CI], 1.9-34.6), New York Heart Association functional class IV (OR, 4.1; CI, 1.0-16.4), and schooling >8 years (OR, 0.2; CI, 0.0-0.8). Adjusting for history of CVA or TIA or excluding patients with a history of CVA or TIA did not affect the findings. Cognitive impairment is frequent in patients hospitalized for CHF decompensation whether or not they have a past history of CVA or TIA. The severity of cognitive impairment parallels that of CHF. The question of whether this cognitive impairment decreases adherence to treatment and contributes to a worse outcome in CHF patients should be explored.