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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. 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. Multifactorially adjusted hazard ratios for low versus high physical activity at leisure time was 1.60 (95% confidence interval 1.40–1.83) for non-Alzheimer's dementia and 0.94 (0.80–1.11) for Alzheimer's disease. Corresponding values for non-Alzheimer's dementia after additional adjustment for physical activity at work or apolipoprotein E (APOE) genotype were 1.60 (1.40–1.83) and 1.82 (1.34–2.15). Multifactorially and APOE adjusted hazard ratios for high versus low physical activity at work were 1.50 (1.10–2.05) for non-Alzheimer's dementia and 1.62 (1.14–2.31) for Alzheimer's disease. When combining the two types of physical activity, physical activity in leisure time had the strongest relationship with risk of non-Alzheimer's dementia. Physical inactivity in leisure time was associated with increased risk of non-Alzheimer's dementia, independent of modifiable risk factors and physical activity at work. The present study thus provides evidence for public health advice on physical activity in leisure time for the vascular part of dementia. [Display omitted] • Prospective study including 117,616 individuals from the general Danish population. • Up to 43 years of follow-up with no losses to follow-up. • Low leisure physical activity associates with high risk of non-Alzheimer's dementia. • Leisure versus work physical activity is superior in predicting risk. • Public health advice on physical activity may prevent non-Alzheimer's dementia. [ABSTRACT FROM AUTHOR]

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. Occasionally, the need for a diagnostic algorithm can be subacute, where surgery has to be postponed until an explanation for the isolated, prolonged APTT has been established. Activated partial thromboplastin time as a coagulation test was developed to monitor patients with hemophilia. Different APTT reagents display considerable differences in their sensitivity to deficiencies of coagulation factors. An isolated, prolonged APTT is seen in (a) individuals/patients with lupus anticoagulants, (b) patients in treatment with anticoagulants, mainly heparin, and (c) patients with deficiencies of specific coagulation factors. In this tutorial review, we summarize what may cause an isolated prolonged APTT and we present a simple diagnostic algorithm to differentiate between lupus anticoagulants (common) and factor deficiencies (rare). The identification of an isolated prolonged APTT as well as the underlying cause can be of the utmost importance in ensuring the correct therapeutic follow‐up. [ABSTRACT FROM AUTHOR]

Dementia is one of the major causes of disability in later life, and ischemic heart disease is a leading cause of morbidity and mortality. Apolipoprotein E (apoE) plays a pivotal role in lipoprotein metabolism in the brain and in the periphery, and is implicated in both dementia and ischemic heart disease. Peripherally, liver-derived apoE is the main source of plasma apoE. Approximately half of plasma apoE is associated with triglyceride-rich lipoproteins, where apoE serves as the main ligand for the low density lipoprotein (LDL) receptor and the LDL receptor Related Protein (LRP). In the brain, apoE is produced mainly by astrocytes. Astrocyte-derived apoE is pivotal for cerebral cholesterol metabolism and clearance of β-amyloid, a major pathological hallmark of Alzheimer disease. Plasma levels of apoE and other lipids and lipoproteins are under strong genetic influence by the APOE polymorphism, and the ε4 allele is a strong genetic risk factor for Alzheimer disease. The characteristics of the APOE polymorphism thus suggest the qualitative importance of apoE, whereas studies of familial absolute apoE deficiency suggest a quantitative importance of plasma apoE levels in lipid metabolism. Whether plasma levels of apoE are associated with increased risk of dementia and ischemic heart disease, and whether these associations are independent of the APOE polymorphism and of lipids and lipoproteins has only recently been established. The aim of this review is to summarize and discuss the current epidemiological and biological evidence for an association of plasma levels of apoE with risk of dementia and ischemic heart disease. [ABSTRACT FROM AUTHOR]

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. Methods: We conducted a three‐stage study to evaluate whether NEUT‐RI could be utilized to screen for misclassified IG% results defined as the manual differential estimating a 10 percentage points higher IG% compared with the automated Sysmex differential. First, 124 patient samples were selected for 800‐cell manual smear analysis based on their NEUT‐RI values and compared with the automatic Sysmex IG% results. Next, 11 098 routine 110‐cell manual smear analyses were compared with the corresponding Sysmex IG% results. Finally, during a 19‐day period 160 additional patient samples underwent smear based on NEUT‐RI values ≥56 fluorescence intensity (FI) to screen for misclassified results beyond our current smear practice. Results: NEUT‐RI ≥56 predicted IG% misclassification with 91% sensitivity and 88% specificity, but primarily when the internal Sysmex flag "Abnormal WBC Scattergram" was present. 90.1% of misclassified results were identified by this flag. Beyond our existing smear rules including this flag, NEUT‐RI ≥56 FI had a positive predictive value below 1%. Conclusion: Both NEUT‐RI and the internal Sysmex flag "Abnormal WBC Scattergram" work well to identify cases of IG% misclassification. However, in our setting NEUT‐RI ≥56 FI had no meaningful additional predictive capacity to identify misclassifications beyond our current smear rules. [ABSTRACT FROM AUTHOR]

Background: Clusterin, also known as apolipoprotein J (apoJ), is one of the most abundantly expressed apolipoproteins in the brain after apolipoprotein E (apoE). Like the ε4 allele of the apolipoprotein E gene (APOE), the clusterin gene (CLU) is a risk locus for Alzheimer's disease, and may play additional roles in atherosclerosis pathogenesis. We tested whether genetic variation in CLU was associated with either Alzheimer's disease or atherosclerosis-related diseases.Methods: We studied individual data on 103,987 participants from the Copenhagen General Population Study (CGPS) and the Copenhagen City Heart Study (CCHS). We genotyped a common CLU variant (rs9331896) and two common APOE variants (rs7412 and rs429358), defining the ε2, ε3, and ε4, alleles in CGPS and CCHS. All individuals in the CGPS and CCHS cohorts were followed from study inclusion to occurrence of event, death, emigration, or until 10 November 2014, whichever came first. Summary consortia data on 258,351 individuals from the International Genomics of Alzheimer's Project (IGAP) and the Coronary Artery Disease Genome-wide Replication and Meta-analysis plus the Coronary Artery Disease (C4D) Genetics and 1000-Genomes-based genome-wide association studies (CARDIoGRAMplusC4D) were used in meta-analyses.Results: In CGPS and CCHS, multifactorially adjusted hazard ratios for Alzheimer's disease, all dementia, vascular dementia, ischemic cerebrovascular disease, and ischemic heart disease were 1.18 (1.07-1.30), 1.09 (1.02-1.17), 0.96 (0.80-1.17), 1.02 (0.97-1.07), and 0.97 (0.93-1.01) per T allele, respectively. Multifactorially adjusted hazard ratios for Alzheimer's disease and all dementia were 2.72 (2.45-3.01) and 2.21 (2.05-2.38) for the APOE ɛ4 allele. There was no interaction between rs9331896 in CLU and rs429358 (defining the ɛ4 allele) in APOE in predicting Alzheimer's disease or all dementia (P = 0.39 and P = 0.21). In a meta-analysis including consortium data, the overall fixed- and random-effects odds ratios for Alzheimer's disease per T allele were 1.16 (1.13-1.18) (I 2 = 0.0%; P for heterogeneity = 0.89).Conclusions: A common variant in CLU was associated with a high risk of Alzheimer's disease and all dementia in the general population but not with vascular dementia or ischemic vascular disease. Important novel aspects compared to previous studies are the incorporation of individual risk factor data, the exact causative ε4 allele, and several subtypes of dementia and atherosclerosis-related endpoints. [ABSTRACT FROM AUTHOR]