Cardiovascular risk factors and aortic valve stenosis: towards 10-year absolute risk charts for primary prevention.

Aim: Due to aging populations the incidence of aortic valve stenosis (AVS) is increasing steeply. Since no medical therapy is available but only surgical interventions, it is highly warranted to identify modifiable risk factors for early prevention. The aim of the study was to investigate the associations of cardiovascular risk factors with AVS and to create 10-year absolute risk scores for use in primary prevention.

The days we never forget: Flashbulb memories across the life span in Alzheimer's disease.

Alzheimer's disease (AD) is characterized by autobiographical memory deficits, with the ability to retrieve episodic-rich memories being particularly affected. Here, we investigated the influence of AD on a specific subtype of episodic memories known as flashbulb memories (i.e.

The current state of apolipoprotein E in dyslipidemia.

Purpose Of Review: Apolipoprotein E (apoE) plays a pivotal role in lipid metabolism in the peripheral circulation and in the brain. This has been recognized for decades; however, the importance of the full spectrum of variation in the APOE gene has been less investigated. This review focusses on current progresses in this field with main focus on apoE in dyslipidemia and vascular disease.

Neutrophil Reactivity Intensity and misclassification of immature granulocytes.

Introduction: Immature granulocyte percentage (IG%) is an important biomarker for infection control. We observed spurious cases where the IG% was dramatically underestimated on the automated Sysmex XN-series hehmatology analyzer compared with manual differential. These cases were associated with high values of "Neutrophil Reactivity Intensity" (NEUT-RI), which should reflect the metabolic activity of the neutrophils.

APOE and vascular disease: Sequencing and genotyping in general population cohorts.

Background And Aims: The apolipoprotein E(APOE) ϵ2/ϵ3/ϵ4 polymorphism plays a central role in lipid metabolism, vascular disease and dementia. The impact of the full range of structural genetic variation in APOE for lipids, lipoproteins and apolipoproteins and for vascular disease in the general population is not known.

Methods: We systematically sequenced APOE in 10,296 individuals from the Copenhagen City Heart Study and genotyped nine rare variants (frequency≥2/10,296) in 95,227 individuals from the Copenhagen General Population Study.

Remembering a life: an examination of open-ended life stories and the reminiscence bump in patients with Alzheimer's disease.

Autobiographical memory impairments are prominent in Alzheimer's disease (AD). Yet, life narratives of AD patients are scarcely examined. Here, twenty-one older adults diagnosed with probably AD and 22 age-matched healthy controls told their life story, and dated the events mentioned in these narratives.

Associations of Alzheimer Disease-Protective APOE Variants With Age-Related Macular Degeneration.

Importance: The association of major lipid genes with and their potential as drug targets for age-related macular degeneration (AMD) is unknown. These associations are important to study because AMD is the leading cause of irreversible late-onset blindness in high-income countries.

Objective: To determine whether the full range of structural genetic variation in apolipoprotein E (APOE), a master gene in peripheral and cerebral lipid metabolism, is associated with risk of AMD.

Physical activity in leisure time and at work and risk of dementia: A prospective cohort study of 117,616 individuals.

Background And Aims: Up to 40% of all dementia cases may be preventable, primarily by treating or acting on well-established cardiovascular risk factors such as diabetes, hypertension, smoking, and physical inactivity. Whether physical inactivity is associated with risk of non-Alzheimer's dementia - a disease influenced by cardiovascular risk factors - and whether a given association differs for physical activity in leisure time and at work remains unknown.

Methods: We conducted a prospective cohort study including 117,616 individuals from the Copenhagen General Population Study and the Copenhagen City Heart Study with up to 43 years of follow-up.

Impact of diet on ten-year absolute cardiovascular risk in a prospective cohort of 94 321 individuals: A tool for implementation of healthy diets.

Background: An unhealthy diet is a major risk factor for cardiovascular disease attributing to the burden of non-communicable diseases. Current dietary guidelines are not sufficiently implemented and effective strategies to encourage people to change and maintain healthy diets are lacking. We aimed to evaluate the impact of incorporating dietary assessment into ten-year absolute risk charts for atherosclerotic cardiovascular disease (ASCVD).

Deficient semantic knowledge of the life course-Examining the cultural life script in Alzheimer's disease.

Cultural life scripts are culturally transmitted semantic knowledge of the expected order and timing of major transitional events in a prototypical life course. This cognitive schema has been shown to serve as an important mnemonic template that guides retrieval from autobiographical memory, especially for positive and important life events. Autobiographical memory deficits are one of the earliest and most prominent symptoms in Alzheimer's disease (AD).

Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals.

Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.

Impact of cardiovascular risk factors and genetics on 10-year absolute risk of dementia: risk charts for targeted prevention.

Aims: Dementia is a major global challenge for health and social care in aging populations. A third of all dementia may be preventable due to cardiovascular risk factors. Intensive multi-domain intervention trials targeting primarily cardiovascular risk factors show improved cognitive function in people at risk.

Dickkopf-1 Overexpression in vitro Nominates Candidate Blood Biomarkers Relating to Alzheimer's Disease Pathology.

Background: Previous studies suggest that Dickkopf-1 (DKK1), an inhibitor of Wnt signaling, plays a role in amyloid-induced toxicity and hence Alzheimer's disease (AD). However, the effect of DKK1 expression on protein expression, and whether such proteins are altered in disease, is unknown.

Objective: We aim to test whether DKK1 induced protein signature obtained in vitro were associated with markers of AD pathology as used in the amyloid/tau/neurodegeneration (ATN) framework as well as with clinical outcomes.

Complement C3 and allergic asthma: a cohort study of the general population.

Complement C3 plays a role in asthma development and severity. We tested the hypothesis that high plasma complement C3 concentration is associated with high risks of asthma hospitalisation and exacerbation.We prospectively assessed the risk of asthma hospitalisation in 101 029 individuals from the Copenhagen General Population Study with baseline measurements of plasma complement C3, and genotyped for rs1065489, rs429608 and rs448260 determining levels of complement C3.

APOE and dementia - resequencing and genotyping in 105,597 individuals.

Introduction: The mechanism behind the strong association between the ɛ2/ɛ3/ɛ4 apolipoprotein E gene (APOE) polymorphism and Alzheimer's disease is not well-characterized. Because low plasma levels of apoE associate with risk of dementia, genetic variants altering apoE levels in general may also associate with dementia.

Methods: The APOE gene was sequenced in 10,369 individuals, and nine amino acid-changing variants with frequencies ≥2/10,000 were further genotyped in 95,228 individuals.

Socioeconomic Consequences of Traumatic Brain Injury: A Danish Nationwide Register-Based Study.

This study examined if acquiring a traumatic brain injury (TBI) increases utilization of health care costs, increases risk of job loss for the patient and the closest relatives, and increases the risk of divorce 1 to 5 years following the injury. The study was conducted as a Danish national population-based register study with follow-up. Participants included a cohort of patients with TBI ( = 18,328) admitted to a hospital or treated in an emergency room (ER) and a matching control group ( = 89,155).

Unexpected, isolated activated partial thromboplastin time prolongation: A practical mini-review.

A common inquiry in coagulation laboratories is how to interpret an unexpected, isolated prolonged activated partial thromboplastin time (APTT). In this context, isolated means together with a normal prothrombin time (PT) and/or normal international normalized ratio (INR). This finding may lead to contact with laboratory doctors for further advice on a diagnostic strategy.

Processed meat intake and chronic disease morbidity and mortality: An overview of systematic reviews and meta-analyses.

Despite the nutritional value of meat, a large volume of reviews and meta-analyses suggests that processed meat intake is associated with an increased risk of chronic diseases. However, assessments of the quality of these published reviews internal validity are generally lacking. We systematically reviewed and assessed the quality alongside summarizing the results of previously published systematic reviews and meta-analyses that examined the association between processed meat intake and cancers, type II diabetes (T2D), and cardiovascular diseases (CVD).

Observational and genetic studies of short telomeres and Alzheimer's disease in 67,000 and 152,000 individuals: a Mendelian randomization study.

Short telomeres might lead to increased risk of Alzheimer's disease, but observational analyses have been inconclusive and potentially confounded by the strong association of both telomere length and risk of Alzheimer's disease with age and adverse lifestyle. To circumvent this, analyses including single nucleotide polymorphisms associated with telomere length used in an instrumental variable analysis produces risk estimates likely free of distortions from reverse causation and of most confounding. We tested the hypothesis that short telomeres are associated with increased risk of Alzheimer's disease, observationally and causal, genetically.

Plasma levels of apolipoprotein E, APOE genotype, and all-cause and cause-specific mortality in 105 949 individuals from a white general population cohort.

Aims: To determine whether plasma apoE levels and APOE genotype are associated with all-cause and cause-specific mortality.

Methods And Results: Using a prospective cohort design with 105 949 white individuals from the general population, we tested the association between plasma apoE at study enrolment and death during follow-up, and whether this was independent of APOE genotype. We confirmed the well-known association between APOE genotypes and mortality.

Blood-brain barrier transcytosis genes, risk of dementia and stroke: a prospective cohort study of 74,754 individuals.

To test whether genetic variants in PICALM, BIN1, CD2AP, and RIN3-suggested to be involved in blood-brain barrier amyloid-β transcytosis pathways-associate with Alzheimer's disease, all dementia, suggested vascular dementia, and stroke, and whether such associations are independent of the strong ε4 APOE risk allele. In a prospective cohort study of 74,754 individuals from the general population we genotyped PICALM (rs10792832), BIN1 (rs6733839), CD2AP (rs10948363), and RIN3 (rs10498633), and generated a weighted and a simple allele score. Multifactorially adjusted hazard ratios for the fourth quartile versus the first quartile of the weighted allele score were 1.

An updated Alzheimer hypothesis: Complement C3 and risk of Alzheimer's disease-A cohort study of 95,442 individuals.

Introduction: We tested the hypothesis that low plasma complement C3 is observationally and genetically associated with high risk of Alzheimer's disease (AD).

Methods: We studied 95,442 individuals enrolled in the Copenhagen General Population Study. In genetic analyses, we further included 8367 individuals from the Copenhagen City Heart Study.