Association of branched-chain amino acids and other circulating metabolites with risk of incident dementia and Alzheimer's disease: A prospective study in eight cohorts

Introduction: Metabolite, lipid, and lipoprotein lipid profiling can provide novel insights into mechanisms underlying incident dementia and Alzheimer's disease. Methods: We studied eight prospective cohorts with 22,623 participants profiled by n

High-throughput quantification of circulating metabolites improves prediction of subclinical atherosclerosis

Aims High-throughput metabolite quantification holds promise for cardiovascular risk assessment. Here, we evaluated whether metabolite quantification by nuclear magnetic resonance (NMR) improves prediction of subclinical atherosclerosis in comparison to conventional lipid testing. Methods and resultsCirculating lipids, lipoprotein subclasses, and small molecules were assayed by NMR for 1595 individuals aged 2439 years from the population-based Cardiovascular Risk in Young Finns Study. Carotid intimamedia thickness (IMT), a marker of subclinical atherosclerosis, was measured in 2001 and 2007. Baseline conventional risk factors and systemic metabolites were used to predict 6-year incidence of high IMT (<90th percentile) or plaque. The best prediction of high intimamedia thickness was achieved when total and HDL cholesterol were replaced by NMR-determined LDL cholesterol and medium HDL, docosahexaenoic acid, and tyrosine in prediction models with risk factors from the Framingham risk score. The extended prediction model improved risk stratification beyond established risk factors alone; area under the receiver operating characteristic curve 0.764 vs. 0.737, P=0.02, and net reclassification index 17.6, P=0.0008. Higher docosahexaenoic acid levels were associated with decreased risk for incident high IMT (odds ratio: 0.74; 95 confidence interval: 0.670.98; P=0.007). Tyrosine (1.33; 1.101.60; P=0.003) and glutamine (1.38; 1.131.68; P=0.001) levels were associated with 6-year incident high IMT independent of lipid measures. Furthermore, these amino acids were cross-sectionally associated with carotid IMT and the presence of angiographically ascertained coronary artery disease in independent populations. ConclusionHigh-throughput metabolite quantification, with new systemic biomarkers, improved risk stratification for subclinical atherosclerosis in comparison to conventional lipids and could potentially be useful for early cardiovascular risk assessment

Digital education for all:multi-university study of increasing competent student admissions at scale

Abstract An indubitable way to put learning at scale in practice is to implement Massive Open Online Courses, or MOOCs. When a wide-enough portfolio of them is available, new applications arise. For instance, university admissions in Finland, where this study was conducted, have traditionally been based on students’ grades in high school studies, an entrance examination, or a combination of both. A minority of students have been accepted through an open university admission path where students can get a study right if they complete enough university course credits with a high enough grade in a given time frame. In this work, we report results from a multi-university project in which the open university admission path has been expanded. All the universities in the Digital Education For All (DEFA) project remarkably expanded their portfolio of MOOCs that were offered both openly and for free, and the new admission path was simultaneously actively marketed and modified. In our analysis, we focus on examining whether the project increased computer science enrolments in the participating universities and how students accepted through the project perform in their studies compared to their peers accepted through other, traditional intake paths

Association of branched-chain amino acids and other circulating metabolites with risk of incident dementia and Alzheimer's disease : A prospective study in eight cohorts

Introduction: Metabolite, lipid, and lipoprotein lipid profiling can provide novel insights into mechanisms underlying incident dementia and Alzheimer's disease. Methods: We studied eight prospective cohorts with 22,623 participants profiled by nuclear magnetic resonance or mass spectrometry metabolomics. Four cohorts were used for discovery with replication undertaken in the other four to avoid false positives. For metabolites that survived replication, combined association results are presented. Results: Over 246,698 person-years, 995 and 745 cases of incident dementia and Alzheimer's disease were detected, respectively. Three branched-chain amino acids (isoleucine, leucine, and valine), creatinine and two very low density lipoprotein (VLDL)-specific lipoprotein lipid subclasses were associated with lower dementia risk. One high density lipoprotein (HDL; the concentration of cholesterol esters relative to total lipids in large HDL) and one VLDL (total cholesterol to total lipids ratio in very large VLDL) lipoprotein lipid subclass was associated with increased dementia risk. Branched-chain amino acids were also associated with decreased Alzheimer's disease risk and the concentration of cholesterol esters relative to total lipids in large HDL with increased Alzheimer's disease risk. Discussion: Further studies can clarify whether these molecules play a causal role in dementia pathogenesis or are merely markers of early pathology. (C) 2018 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association.Peer reviewe

Circulating metabolites and general cognitive ability and dementia: Evidence from 11 cohort studies

Introduction: Identifying circulating metabolites that are associated with cognition and dementia may improve our understanding of the pathogenesis of dementia and provide crucial readouts for preventive and therapeutic interventions. Methods: We studied 299 metabolites in relation to cognition (general cognitive ability) in two discovery cohorts (N total = 5658). Metabolites significantly associated with cognition after adjusting for multiple testing were replicated in four independent cohorts (N total = 6652), and the associations with dementia and Alzheimer's disease (N = 25,872) and lifestyle factors (N = 5168) were examined. Results: We discovered and replicated 15 metabolites associated with cognition including subfractions of high-density lipoprotein, docosahexaenoic acid, ornithine, glutamine, and glycoprotein acetyls. These associations were independent of classical risk factors including high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, and apolipoprotein E (APOE) genotypes. Six of the cognition-associated metabolites were related to the risk of dementia and lifestyle factors. Discussion: Circulating metabolites were consistently associated with cognition, dementia, and lifestyle factors, opening new avenues for prevention of cognitive decline and dementia. (C) 2018 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association