Lower Performance in Orientation to Time and Place Associates with Greater Risk of Cardiovascular Events and Mortality in the Oldest Old: Leiden 85-Plus Study

Background: Impairment in orientation to time and place is commonly observed in community-dwelling older individuals. Nevertheless, the clinical significance of this has been not fully explored. In this study, we investigated the link between performance in orientation domains and future risk of cardiovascular events and mortality in a non-hospital setting of the oldest old adults.Methods: We included 528 subjects free of myocardial infarction (Group A), 477 individuals free of stroke/transient ischemic attack (Group B), and 432 subjects free of both myocardial infarction and stroke/transient ischemic attack (Group C) at baseline from the population-based Leiden 85-plus cohort study. Participants were asked to answer five questions related to orientation to time and five questions related to orientation to place. 5-year risks of first-time fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, as well as cardiovascular and non-cardiovascular mortality, were estimated using the multivariate Cox regression analysis.Results: In the multivariable analyses, adjusted for sociodemographic characteristics and cardiovascular risk factors, each point lower performance in “orientation to time” was significantly associated with higher risk of first-time myocardial infarction (hazard ratio [HR] 1.35, 95% confidence interval [CI] 1.09–1.67, P = 0.007), first-time stroke (HR 1.35, 95% CI 1.12–1.64, P = 0.002), cardiovascular mortality (HR 1.28, 95% CI 1.06–1.54, P = 0.009) and non-cardiovascular mortality (HR 1.37, 95% CI 1.20–1.56, P < 0.001). Similarly, each point lower performance in “orientation to place” was significantly associated with higher risk of first-time myocardial infarction (HR 1.67, 95% CI 1.25–2.22, P = 0.001), first-time stroke (HR 1.39, 95% CI 1.05–1.82, P = 0.016), cardiovascular mortality (HR 1.35, 95% CI 1.00–1.82, P = 0.054) and non-cardiovascular mortality (HR 1.45, 95% CI 1.20–1.77, P < 0.001).Conclusions: Lower performance in orientation to time and place in advanced age is independently related to higher risk of myocardial infarction, stroke and mortality. Impaired orientation might be an early sign of covert vascular injuries, putting subjects at greater risk of cardiovascular events and mortality

Cognitive function in dementia-free subjects and survival in old Age: The PROSPER study

Impairment in domain-specific cognitive function is associated with the increased risk of mortality. We prospectively evaluated the association of executive function and memory with the risk of long-term mortality in dementia-free older subjects. Moreover, we investigated the role of structural brain abnormalities in this association. We included 547 dementia-free participants (mean age 78years, 56.5% male) from the nested magnetic resonance imaging sub-study of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). Cox proportional hazard models were used to model 10-year risk of all-cause, cardiovascular and non-cardiovascular mortality in relation to performance in executive function and memory. Moreover, we evaluated the role of total brain parenchymal volume, cerebral blood flow, white matter hyperintensity and the presence of microbleeds and infarcts in the link between cognitive function and mortality. In the multivariable model, lower performance in executive function was associated with greater risk of all-cause (hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.31-1.70), cardiovascular (HR 1.69, 95%CI 1.36-2.11) and non-cardiovascular (HR 1.36, 95%CI 1.15-1.62) mortality. Similarly, poorer performance in memory tests associated with higher risk of all-cause (HR 1.47, 95%CI 1.29-1.68), cardiovascular (HR 1.45, 95%CI 1.15-1.83) and non-cardiovascular (HR 1.49, 95%CI 1.27-1.76) mortality. The associations were similar in subjects with various levels of brain structural abnormalities and cerebral blood flow (all p for interaction >0.05). Poorer performance in both executive function and memory tests associates with all-cause, cardiovascular and non-cardiovascular mortality in elderly individuals. This association is independent of cardiovascular risk factors and diseases, brain structural abnormalities and cerebral blood flow

Levels of Blood Biomarkers among Patients with Myocardial Infarction in Comparison to Control Group

BACKGROUND: Myocardial infarction (MI) as a term for a heart attack happens due to reduced blood flow to heart myocardium and lack of oxygen supply caused by plaques inthe interior walls of coronary arteries. With respect to the importance of MI etiology, we aimed to study the relationship of MI and blood examination variables.METHODS: This study was conducted in Mazandaran Heart Center as a hospital-based case-control Comprising 894 participants including 465 cases and 429 controls, individually matched by sex and age. Considered blood markers were analyzed using routine laboratory methods and equipment.RESULTS: Of all participants, 64.3% of the cases and 51.0% of the controls were males with a mean age of 61.2 (±13.8) in cases and 62.4 (±14.) in controls. We could not find any differences between cases and controls for total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and alkaline-phosphatase (ALP) (P>0.05). However, levels of creatine-kinase-muscle/brain (CK-MB) (P<0.0001), fasting-blood-sugar (FBS) (P<0.0001), aspartateaminotransferase (AST) (P<0.0001), alanine-transferase (ALT) (P<0.0001) and erythrocyte sedimentation rate (ESR) (P=0.001) were significantly higher in cases compared to the controls (P<0.05). Multivariable analyses revealed that the risk of MI was associated with high levels of AST (adjusted OR=24.3, 95%CI=3.5±165.6, P=0.001) and LDL (adjusted OR=7.4, 95%CI=1.0±51.8, P=0.001).CONCLUSION: Our investigation indicated that the levels of CK-MB, FBS, AST, ALT and ESR were significantly higher in patients with MI. Besides, our findings showed that the risk of MI in cases with high levels of AST and LDL was about 24 and 7 times more than the control group respectively

Mapping development and health effects of cooking with solid fuels in low-income and middle-income countries, 2000-18 : a geospatial modelling study

Background More than 3 billion people do not have access to clean energy and primarily use solid fuels to cook. Use of solid fuels generates household air pollution, which was associated with more than 2 million deaths in 2019. Although local patterns in cooking vary systematically, subnational trends in use of solid fuels have yet to be comprehensively analysed. We estimated the prevalence of solid-fuel use with high spatial resolution to explore subnational inequalities, assess local progress, and assess the effects on health in low-income and middle-income countries (LMICs) without universal access to clean fuels.Methods We did a geospatial modelling study to map the prevalence of solid-fuel use for cooking at a 5 km x 5 km resolution in 98 LMICs based on 2.1 million household observations of the primary cooking fuel used from 663 population-based household surveys over the years 2000 to 2018. We use observed temporal patterns to forecast household air pollution in 2030 and to assess the probability of attaining the Sustainable Development Goal (SDG) target indicator for clean cooking. We aligned our estimates of household air pollution to geospatial estimates of ambient air pollution to establish the risk transition occurring in LMICs. Finally, we quantified the effect of residual primary solid-fuel use for cooking on child health by doing a counterfactual risk assessment to estimate the proportion of deaths from lower respiratory tract infections in children younger than 5 years that could be associated with household air pollution.Findings Although primary reliance on solid-fuel use for cooking has declined globally, it remains widespread. 593 million people live in districts where the prevalence of solid-fuel use for cooking exceeds 95%. 66% of people in LMICs live in districts that are not on track to meet the SDG target for universal access to clean energy by 2030. Household air pollution continues to be a major contributor to particulate exposure in LMICs, and rising ambient air pollution is undermining potential gains from reductions in the prevalence of solid-fuel use for cooking in many countries. We estimated that, in 2018, 205000 (95% uncertainty interval 147000-257000) children younger than 5 years died from lower respiratory tract infections that could be attributed to household air pollution.Interpretation Efforts to accelerate the adoption of clean cooking fuels need to be substantially increased and recalibrated to account for subnational inequalities, because there are substantial opportunities to improve air quality and avert child mortality associated with household air pollution. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.Peer reviewe

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Lower Performance in Orientation to Time and Place Associates with Greater Risk of Cardiovascular Events and Mortality in the Oldest Old: Leiden 85-Plus Study

Pathophysiology, epidemiology and therapy of agein

Chronic phosphodiesterase type 2 inhibition improves memory in the APPswe/PS1dE9 mouse model of Alzheimer's disease

Alzheimer's disease (AD) is characterized by progressive cognitive deficits and synaptic dysfunction. Over the last decade phosphodiesterase inhibitors (PDEIs) have received increasing attention as putative cognition enhancers and have been suggested as a novel treatment strategy for AD. Given their ability to prevent hydrolysis of cAMP and/or cGMP, they can stimulate the cAMP/protein kinase A (PKA)/cAMP element-binding protein (CREB) and cGMP/PKG/CREB pathway to enhance synaptic transmission by increasing CREB phosphorylation (pCREB) and brain-derived neurotrophic factor (BDNF) transcription. Based on previous research, we hypothesized that chronic PDE2I treatment would improve AD-related cognitive deficits, by decreasing amyloid-beta (A beta) plaque load, enhancing pCREB and BDNF levels and increasing synaptic density in the hippocampus of 8-month-old APPswe/PS1dE9 mice. Results indicated that chronic PDE2I treatment could indeed improve memory performance in APPswe/PS1dE9 mice, without affecting anxiety, depressive-like behavior or hypothalamus pituitary adrenal axis regulation. However, no treatment effects were observed on A beta plaque load, pCREB or BDNF concentrations, or presynaptic density in the hippocampus, suggesting that other signaling pathways and/or effector molecules might be responsible for its cognition-enhancing effects. Presynaptic density in the stratum lucidum of the CA3 subregion was significantly higher in APPswe/PS1dE9 mice compared to WT controls. possibly reflecting a compensatory mechanism. In conclusion, PDEs in general, and PDE2 specifically, could be considered as promising therapeutic targets for cognition enhancement in AD, although the underlying mechanism of action remains to be elucidated. This article is part of a Special Issue entitled 'Cognitive Enhancers'

Lower Performance in Orientation to Time and Place Associates with Greater Risk of Cardiovascular Events and Mortality in the Oldest Old: Leiden 85-Plus Study

Pathophysiology, epidemiology and therapy of agein