Un horario laboral prolongado se vincula con un mayor riesgo de ictus

Association Between Reported Long Working Hours and History of Stroke in the CONSTANCES

Abstract

Background and Purpose

Long working hours (LWHs) are a potential risk factor for stroke. The aim of this study was to investigate this association in a large general population cohort.

Methods

We used the French population-based cohort, CONSTANCES (Cohorte des Consultants des Centres d'Examens de Santé), to retrieve information on age, sex, smoking, and working hours from the baseline, self-administered questionnaire. Other cardiovascular risk factors and previous occurrence of stroke were taken from a parallel medical interview. We defined LWH as working time >10 hours daily for at least 50 days per year. Participants with primarily part-time jobs were excluded as were those with stroke before LWH exposure. We used logistic models to estimate the association between LWH and stroke, stratified by age, sex, and occupation. In additional modeling, we excluded subjects whose stroke occurred within 5 years of the first reported work exposure.

Results

Among the 143 592 participants in the analyses, there were 1224 (0.9%) strokes, 42 542 (29.6%) reported LWH, and 14 481 (10.1%) reported LWH for 10 years or more. LWH was associated with an increased risk of stroke: adjusted odds ratio of 1.29 (95% CI, 1.11–1.49). Being exposed to LWH for 10 years or more was more strongly associated with stroke, adjusted odds ratio of 1.45 (95% CI, 1.21–1.74). The association showed no differences between men and women but was stronger in white-collar workers under 50 years of age.

Conclusions

This large analysis reveals a significant association between stroke and exposure to LWH for 10 years or more. The findings are relevant for individual and global prevention.

Stroke is a devastating though largely preventable health condition.1 Long working hours (LWH) may be a risk factor for cardiovascular diseases and stroke.2 In Japan, 60% of compensated Karoshi (death from over-work) cases died of stroke.3 A meta-analysis observed a dose-response relationship between LWH and stroke but did not adjust for other modifiable risk factors of stroke.4 A Danish study found association with LWH only for hemorrhagic stroke.5

Our study investigated the association between LWH and stroke in a large general population study.

References

1. Feigin VL, Roth GA, Naghavi M, Parmar P, Krishnamurthi R, Chugh S, et al.; Global Burden of Diseases, Injuries and Risk Factors Study 2013 and Stroke Experts Writing Group. Global burden of stroke and risk factors in 188 countries, during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.Lancet Neurol. 2016; 15:913–924.

2. van der Hulst M. Long workhours and health.Scand J Work Environ Health. 2003; 29:171–188.

3. Ke DS. Overwork, stroke, and karoshi-death from overwork.Acta Neurol Taiwan. 2012; 21:54–59.

4. Kivimäki M, Jokela M, Nyberg ST, Singh-Manoux A, Fransson EI, Alfredsson L, et al.; IPD-Work Consortium. Long working hours and risk of coronary heart disease and stroke: a systematic review and meta-analysis of published and unpublished data for 603,838 individuals.Lancet. 2015; 386:1739–1746. doi: 10.1016/S0140-6736(15)60295-1.

5. Hannerz H, Albertsen K, Burr H, Nielsen ML, Garde AH, Larsen AD, et al.. Long working hours and stroke among employees in the general workforce of Denmark.Scand J Public Health. 2018; 46:368–374.

Personas con trastorno límite de la personalidad activan regiones cerebrales distintas para controlar sus impulsos

Response inhibition in borderline personality disorder: Neural and behavioral correlates

Abstract

Although response inhibition is thought to be important in borderline personality disorder (BPD), little is known about its neurophysiological basis. This study aimed to provide insight into this issue by capitalizaing on the high temporal resolution of electroencephalography and information provided by source localization methods. To this end, twenty unmedicated patients with BPD and 20 healthy control subjects performed a modified go/no-go task designed to better isolate the brain activity specifically associated with response inhibition. Event-related potentials (ERP) were measured and further analyzed at the scalp and source levels. Patients with BPD made more commission errors (failed inhibitions) than control subjects. Scalp ERP data showed that both groups displayed greater frontocentral P3 amplitude for no-go (response inhbition) than for go trials (response execution). However, source reconstruction data revealed that patients with BPD activated posterior parietal regions (precuneus) to inhibit their responses, whereas controls activated prefrontal regions (presupplementary motor area, preSMA). This dissociation was supported by a significant Region (precuneus, preSMA) x Trial Type (no-go, go) x Group (BPD, control) interaction. These findings extend our understanding of the neurophysiological basis of abnormal response inhibition in BPD, suggesting that patients with BPD recruit different brain regions for inhibiting prepotent responses compared to controls. Future research in larger, medication-naïve samples of patients with BPD is required to confirm and extend these findings.

Síntomas depresivos y sobrecarga en los familiares cuidadores de pacientes con enfermedad de Alzheimer

Depressive symptoms and burden in family caregivers in Alzheimer´s disease: a model of structural equations

El control de la hipertensión reduciría el riesgo de demencia

Effects of Nilvadipine on Cerebral Blood Flow in Patients With Alzheimer Disease

Abstract

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Nuevas evidencias sobre la relación entre la salud del corazón y la del cerebro

Cognitive Decline Before and After Incident Coronary Events

Abstract

Background

Previous studies have suggested that coronary heart disease (CHD) may be associated with accelerated cognitive decline. However, the temporal pattern of cognitive decline before and after incident CHD remains largely unknown.

Objectives

The purpose of this study was to determine the cognitive trajectory before and after incident CHD diagnosis in a national representative cohort age ≥50 years.

Methods

This study included 7,888 participants (mean age 62.1 ± 10.2 years) with no history of stroke or incident stroke during follow-up from the English Longitudinal Study of Ageing. Participants underwent a cognitive assessment at baseline (wave 1, 2002 to 2003), and at least 1 other time point (from wave 2 [2004 to 2005] to wave 8 [2016 to 2017]). Incident CHD was identified as a diagnosis of myocardial infarction and/or angina during follow-up.

Results

Incident CHD was associated with accelerated cognitive decline during a median follow-up of 12 years. The annual rate of cognitive decline before CHD diagnosis among individuals who experienced incident CHD was similar to that of participants who remained CHD-free throughout follow-up. No short-term cognitive decline was observed in participants with CHD diagnosis after the event. In the years following CHD diagnosis, global cognition, verbal memory, and temporal orientation scores declined significantly faster than they did before the event, after multivariable adjustment. Sensitivity analyses yielded similar results.

Conclusions

Incident CHD is associated with accelerated cognitive decline after, but not before, the event. Attention should be drawn to the long-term cognitive deterioration related to CHD. Careful monitoring of cognitive function is warranted in CHD patients in the years following the event.

Estudian los patrones de disparo de las neuronas en el sistema olfativo

Structured spike series specify gene expression patterns for olfactory circuit formation

INTRODUCTION

The development of precise neural circuits is initially directed by genetic programming and subsequently refined by neural activity. In the mouse olfactory system, axons from various olfactory sensory neurons expressing the same olfactory receptor converge onto a few spatially invariant glomeruli, generating the olfactory glomerular map in the olfactory bulbs. During development, olfactory receptors instruct axon sorting to form discrete glomeruli. Olfactory receptors generate a combinatorial code of axon-sorting molecules whose expression is regulated by neural activity. However, it remains unclear how neural activity induces olfactory receptor–specific expression patterns of axon-sorting molecules.

RATIONALE

The prevailing model for the activity-dependent development of neural circuits postulates an interaction between pre- and postsynaptic neurons. In Hebbian plasticity, the correlated activity of pre- and postsynaptic neurons strengthens synaptic connections, whereas uncorrelated activity or lack of activity weakens them. However, this theory does not explain activity-dependent mechanisms in olfactory map formation. Axons of olfactory sensory neurons can converge to form glomerular-like structures even in mutant mice lacking synaptic partners, suggesting another activity-dependent mechanism for glomerular segregation. The involvement of neural activity in olfactory map formation has been demonstrated by experimental suppression of neural activity. Here, we asked how neural activity is involved in the expression of axon-sorting molecules regulating glomerular segregation.

RESULTS

We performed calcium imaging experiments and optogenetic stimulation to address how neural activity generates olfactory receptor–specific expression patterns of axon-sorting molecules. Calcium imaging of olfactory sensory neurons revealed that the temporal patterns of spontaneous neuronal spikes were not spatially organized, but rather were correlated with the olfactory receptor types. Receptor substitution experiments demonstrated that olfactory receptors determine spontaneous activity patterns. Moreover, optogenetically differentiated patterns of neuronal activity induced expression of corresponding axon-sorting molecules and regulated glomerular segregation.

CONCLUSION

We have demonstrated an instructive role of neural activity in olfactory map formation. We propose an activity-dependent mechanism, different from Hebbian plasticity theory, in which specific patterns of spontaneous activity determined by the expressed olfactory receptor type contribute to generating the combinatorial code of axon-sorting molecules for olfactory receptor–specific axon sorting.

Neural activity is involved in various aspects of brain development and function. Our findings show that in the olfactory system, gene expression that regulates neural circuit formation is dependent on neural firing patterns. With this strategy, neurons can generate variation through diversifying gene expression. The pattern-dependent gene regulation may also expand beyond development to plastic changes in neural circuits throughout the lifetime.

Firing pattern–dependent olfactory map formation.

•  Top left: Diverse patterns of spontaneous neural activity in olfactory sensory neurons. Bottom left: A combinatorial expression pattern of axon-sorting molecules at axon termini of olfactory sensory neurons. Right: A model for activity-dependent olfactory map formation. OE, olfactory epithelium; OB, olfactory bulb. Axon-sorting molecules for glomerular segregation: red, Kirrel2 (kin of IRRE-like protein 2); green, Sema7A (semaphorin 7A); blue, PCDH10 (protocadherin 10).

La reserva cognitiva reduciría el riesgo de demencia, aunque no variaría su curso

Cognitive Reserve in Midlife is not Associated with Amyloid-β Deposition in Late-Life

Abstract

We examined associations between cognitive reserve and late-life amyloid-β deposition using florbetapir positron emission tomography (PET). We used data from the Atherosclerosis Risk in Communities (ARIC) and ARIC-PET Study. 330 dementia-free participants underwent PET scans. Mean global cortical standardized uptake value ratio (SUVR) >1.2 was defined as elevated. Midlife cognition was significantly associated with late-life cognition, but not with late-life elevated SUVR; education was not associated with late-life SUVR, but was strongly associated with late-life cognition. Cognitive reserve may reduce dementia risk by mitigating the impact of Alzheimer's disease pathology on the clinical expression of dementia, rather than by altering its pathogenesis.

Correspondence: [*] Correspondence to: Rebecca F. Gottesman, MD, PhD, Departments of Neurology and Epidemiology, Johns Hopkins University, Baltimore, MD, USA. E-mail: rgottesm@jhmi.edu.

Keywords: Amyloid, cohort study, education, epidemiology, human, PET imaging

La obesidad podría empeorar el grado de discapacidad de la esclerosis múltiple remitente recurrente

Obesity worsens central inflammation and disability in multiple sclerosis

Abstract

Background: Previous studies evidenced a link between metabolic dysregulation, inflammation, and neurodegeneration in multiple sclerosis (MS).

Objectives: To explore whether increased adipocyte mass expressed as body mass index (BMI) and increased serum lipids influence cerebrospinal fluid (CSF) inflammation and disease severity.

Methods: In this cross-sectional study, 140 consecutive relapsing-remitting (RR)-MS patients underwent clinical assessment, BMI evaluation, magnetic resonance imaging scan, and blood and CSF collection before any specific drug treatment. The CSF levels of the following cytokines, adipocytokines, and inflammatory factors were measured: interleukin (IL)-6, IL-13, granulocyte macrophage colony-stimulating factor, leptin, ghrelin, osteoprotegerin, osteopontin, plasminogen activator inhibitor-1, resistin, and Annexin A1. Serum levels of triglycerides, total cholesterol (TC), and high-density lipoprotein cholesterol (HDL-C) were assessed.

Results: A positive correlation emerged between BMI and Expanded Disability Status Scale score. Obese RR-MS patients showed higher clinical disability, increased CSF levels of the proinflammatory molecules IL-6 and leptin, and reduced concentrations of the anti-inflammatory cytokine IL-13. Moreover, both the serum levels of triglycerides and TC/HDL-C ratio showed a positive correlation with IL-6 CSF concentrations.

Conclusion: Obesity and altered lipid profile are associated with exacerbated central inflammation and higher clinical disability in RR-MS at the time of diagnosis. Increased adipocytokines and lipids can mediate the negative impact of high adiposity on RR-MS course.Keywords Obesity, adipocytokines, multiple sclerosis, inflammation, serum lipid profile, BMI

Descubren la relación entre las funciones ejecutivas de mujeres con anorexia y un neuropéptido

Reduced Plasma Orexin-A Concentrations are Associated with Cognitive Deficits in Anorexia Nervosa

Abstract
Orexins/hypocretins are neuropeptides implicated in numerous processes, including food intake and cognition. The role of these peptides in the psychopathology of anorexia nervosa (AN) remains poorly understood. The aim of the current study was to evaluate the associations between plasma orexin-A (OXA) concentrations and neuropsychological functioning in adult women with AN, and a matched control group. Fasting plasma OXA concentrations were taken in 51 females with AN and in 51 matched healthy controls. Set-shifting was assessed using the Wisconsin Card Sorting Test (WCST), whereas decision making was measured using the Iowa Gambling Task (IGT). The AN group exhibited lower plasma OXA levels than the HC group. Lower mean scores were obtained on the IGT in AN patients. WCST perseverative errors were significantly higher in the AN group compared to HC. In both the AN and HC group, OXA levels were negatively correlated with WCST non-perseverative errors. Reduced plasma OXA concentrations were found to be associated with set-shifting impairments in AN. Taking into consideration the function of orexins in promoting arousal and cognitive flexibility, future studies should explore whether orexin partly underpins the cognitive impairments found in AN.

Mayor riesgo de neumonía en pacientes con enfermedad de Alzheimer por el consumo de opioides

Hospital-Treated Pneumonia Associated with Opioid Use Among Community Dwellers with Alzheimer’s Disease


Abstract

BACKGROUND:

Pneumonia is a common cause for hospitalization and excess mortality among persons with Alzheimer's disease (AD), but little research exists evaluating drug use as its risk factor.

OBJECTIVE:

We investigated the association between opioid use and hospital-treated pneumonia among community dwellers with AD.

METHODS:

This study was part of the Medication use and Alzheimer's Disease (MEDALZ) cohort. We included all community dwellers newly diagnosed with AD during 2010-2011 in Finland with incident prescription opioid use (n = 5,623) and age-, sex-, and time since AD diagnosis-matched nonusers (n = 5,623). Opioid use data, modelled from pharmacy dispensing data, and hospital-treated pneumonia were retrieved from nationwide registers. Patients with active cancer treatment were excluded. Hazard models compared opioid users to nonusers, adjusting for comorbidities, socioeconomic position. and other drug use.

RESULTS:

Incident opioid use was associated with an increased risk of hospital-treated pneumonia compared to nonuse (adjusted HR, aHR 1.34, 95% CI 1.14-1.57). Highest risk was observed during the first two months of use (aHR 2.58, 95% CI 1.87-3.55). Compared to weak opioids, buprenorphine was not associated with a higher risk of pneumonia (aHR 1.20, 95% CI 0.83-1.76), but strong opioids were (aHR 1.84, 95% CI 1.15-2.97). The risk was higher for those using ≥50 morphine milligram equivalents (MME)/day (aHR 2.03, 95% CI 1.24-3.31), compared to using < 50 MME / day.

CONCLUSIONS:

Opioid use was associated with a risk of hospital-treated pneumonia in a dose-dependent manner among persons with AD. Risk-minimization strategies should be considered if opioid therapy is needed.

KEYWORDS:

Aged; Alzheimer’s disease; dementia; opioids; pharmacoepidemiology; pneumonia

Alteraciones del desarrollo en prematuros tardíos a los dos años de edad

Psychomotor development in late preterms at two years of age: a comparison with full-term newborn infants using two different instruments

INTRODUCTION. 

Late preterm infants currently constitute 70% of preterm infant births. They present greater comorbidity, including neurodevelopment disorders, which may not manifest until the school age. 

AIM. 

To identify the existence of difficulties in the neurodevelopment at the age of two years. 

SUBJECTS AND METHODS. 

The psychomotor development was performed at two years of age in late preterm infants and term control group born at our center between January and September 2014, with Brunet-Lézine Revised test and Ages & Stages Questionnaires (ASQ-3) questionnaire. 

RESULTS. 

88 children were included. Late preterm infants had lower scores in the language area and postural developmental. Girls achieved better results than males at global developmental age, oculo-motor coordination, language area and sociability. The ASQ-3 questionnaire detected differences in communication and socio-individual. Prematurity and male sex were identified as an independent risk factor to present a developmental disorder, prematurity for language impairment and male sex for younger developmental age and language impairment. The correlation between language assessment with the Brunet-Lézine Revised test and the ASQ-3 questionnaire was good, with a Pearson correlation coefficient of 0.7 (p < 0.001), showing the usefulness of the questionnaire. 

CONCLUSIONS. 

Late preterm infants have a lower developmental age in the language area at two years. Prematurity and male sex are risk factors for developmental disorder. Language assessment with the ASQ-3 questionnaire may be a useful tool to detect disorders and intervene early.

Una proteína del líquido cefalorraquídeo, biomarcador fiable de enfermedades priónicas

CSF neurogranin as a neuronal damage marker in CJD: a comparative study with AD

Abstract

Objective 

To investigate whether cerebrospinal fluid (CSF) neurogranin concentrations are altered in sporadic Creutzfeldt-Jakob disease (CJD), comparatively with Alzheimer’s disease (AD), and associated with neuronal degeneration in brain tissue.

Methods 

CSF neurogranin, total tau, neurofilament light (NFL) and 14-3-3 protein were measured in neurological controls (NCs, n=64), AD (n=46) and CJD (n=81). The accuracy of neurogranin discriminating the three diagnostic groups was evaluated. Correlations between neurogranin and neurodegeneration biomarkers, demographic, genetic and clinical data were assessed. Additionally, neurogranin expression in postmortem brain tissue was studied.

Results 

Compared with NC, CSF neurogranin concentrations were increased in CJD (4.75 times of NC; p < 0.001, area under curve (AUC), 0.96 (95% CI 0.93 to 0.99) and AD (1.94 times of NC; p < 0.01, AUC 0.73, 95% CI 0.62 to 0.82), and were able to differentiate CJD from AD (p < 0.001, AUC 0.85, 95% CI 0.78 to 0.92). CSF tau was increased in CJD (41 times of NC) and in AD (3.1 times of NC), both at p < 0.001. In CJD, neurogranin positively correlated with tau (r = 0.55, p < 0.001) and was higher in 14-3-3-positivity (p < 0.05), but showed no association with NFL (r = 0.08, p = 0.46). CJD-MM1/MV1 cases displayed higher neurogranin levels than VV2 cases. Neurogranin was increased at early CJD disease stages and was a good prognostic marker of survival time in CJD. In brain tissue, neurogranin was detected in the cytoplasm, membrane and postsynaptic density fractions of neurons, with reduced levels in AD, and more significantly in CJD, where they correlated with synaptic and axonal markers.

Conclusions 

Neurogranin is a new biomarker of prion pathogenesis with diagnostic and prognostic abilities, which reflects the degree of neuronal damage in brain tissue in a CJD subtype manner.

La diabetes mellitus en la mediana edad incrementaría el riesgo de ictus isquémico años más tarde

Type 2 diabetes in midlife and risk of cerebrovascular disease in late life: a prospective nested case−control study in a nationwide Swedish twin cohort

Abstract

Aims/hypothesis
We aimed to examine the association between midlife type 2 diabetes mellitus and cerebrovascular disease (CBD) in late life, and further to explore whether genetic and early-life familial environmental factors (such as shared childhood socioeconomic status and adolescent environment) play a role in this association.

Methods

In this prospective nested case−control study based on the Swedish Twin Registry, 33,086 twin individuals who were born in 1958 or earlier and were CBD-free before the age of 60 were included. Midlife (40–59 years) type 2 diabetes was ascertained from self-report, the National Patient Registry (NPR) and glucose-lowering medication use. CBD diagnosis (cerebral infarction, occlusion of cerebral arteries, subarachnoid haemorrhage, intracerebral haemorrhage and unspecified CBD) and onset age were identified from the NPR. Late-life CBD was defined as CBD onset age ≥60 years. Generalised estimating equation (GEE) models were used to analyse unmatched case−control data (adjusted for the clustering of twins within a pair). Conditional logistic regression was used in co-twin matched case−control analyses in CBD-discordant twin pairs.

Results

Of all the participants, 1248 (3.8%) had midlife type 2 diabetes and 3121 (9.4%) had CBD in late life. In GEE models adjusted for age, sex, education, BMI, smoking, alcohol consumption, marital status, hypertension and heart disease, the ORs (95% CIs) of type 2 diabetes were 1.29 (1.03, 1.61) for cerebral infarction, 2.03 (1.20, 3.44) for occlusion of cerebral arteries, 0.52 (0.12, 2.21) for subarachnoid haemorrhage and 0.78 (0.45, 1.36) for intracerebral haemorrhage. In multi-adjusted conditional logistic regression, the OR of the type 2 diabetes–cerebral infarction association was 0.96 (0.51, 1.80). The differences in ORs from the GEE and co-twin control analyses were not statistically significant (p = 0.780).

Conclusions/interpretation
Midlife type 2 diabetes is significantly associated with increased risk of cerebral infarction and occlusion of cerebral arteries, but not intracerebral haemorrhage or subarachnoid haemorrhage in late life. Genetic and early-life familial environmental factors do not appear to account for the type 2 diabetes–cerebral infarction association, but further clarification is needed.

Keywords

Cerebrovascular disease Prospective nested case−control study The Swedish twin cohort Type 2 diabetes