Atrial fibrillation is associated with reduced brain volume and cognitive function independent of cerebral infarcts.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Atrial fibrillation (AF) has been associated with cognitive decline independent of stroke, suggesting additional effects of AF on the brain. We aimed to assess the association between AF and brain function and structure in a general elderly population.This is a cross-sectional analysis of 4251 nondemented participants (mean age, 76 ± 5 years) in the population-based Age, Gene/Environment Susceptibility-Reykjavik Study. Medical record data were collected for the presence, subtype, and time from first diagnosis of AF; 330 participants had AF. Brain volume measurements, adjusted for intracranial volume, and presence of cerebral infarcts were determined with magnetic resonance imaging. Memory, speed of processing, and executive function composites were calculated from a cognitive test battery. In a multivariable linear regression model, adjustments were made for demographic factors, cardiovascular risk factors, and cerebral infarcts.Participants with AF had lower total brain volume compared with those without AF (P<0.001). The association was stronger with persistent/permanent than paroxysmal AF and with increased time from the first diagnosis of the disease. Of the brain tissue volumes, AF was associated with lower volume of gray and white matter hyperintensities (P<0.001 and P = 0.008, respectively), but not of white matter hyperintensities (P = 0.49). Participants with AF scored lower on tests of memory.AF is associated with smaller brain volume, and the association is stronger with increasing burden of the arrhythmia. These findings suggest that AF has a cumulative negative effect on the brain independent of cerebral infarcts.Landspitali National University Hospital of Iceland Science Fund Helga Jonsdottir and Sigvaldi Kristjansson Memorial Fund National Institutes of Health/N01-AG-1-2100 National Institute on Aging Intramural Research Program Icelandic Heart Association Althingi (the Icelandic Parliament

Comparison of multiple DNA dyes for real-time PCR: effects of dye concentration and sequence composition on DNA amplification and melting temperature

The importance of real-time polymerase chain reaction (PCR) has increased steadily in clinical applications over the last decade. Many applications utilize SYBR Green I dye to follow the accumulation of amplicons in real time. SYBR Green I has, however, a number of limitations that include the inhibition of PCR, preferential binding to GC-rich sequences and effects on melting curve analysis. Although a few alternative dyes without some of these limitations have been recently proposed, no large-scale investigation into the properties of intercalating dyes has been performed. In this study, we investigate 15 different intercalating DNA dyes for their inhibitory effects on PCR, effects on DNA melting temperature and possible preferential binding to GC-rich sequences. Our results demonstrated that in contrast to the results of SYBR Green I, two intercalating dyes SYTO-13 and SYTO-82 do not inhibit PCR, show no preferential binding to GC rich sequences and do not influence melting temperature, Tm, even at high concentrations. In addition, SYTO-82 demonstrated a 50-fold lower detection limit in a dilution series assay. In conclusion, the properties of SYTO-82 and SYTO-13 will simplify the development of multiplex assays and increase the sensitivity of real-time PCR

Genome-wide association studies of cerebral white matter lesion burden: The CHARGE consortium

White matter hyperintensities (WMH) detectable by magnetic resonance imaging (MRI)are part of the spectrum of vascular injury associated with aging of the brain and are thought to reflect ischemic damage to the small deep cerebral vessels. WMH are associated with an increased risk of cognitive and motor dysfunction, dementia, depression, and stroke. Despite a significant heritability, few genetic loci influencing WMH burden have been identified

Heterogeneity in white blood cells has potential to confound DNA methylation measurements.

Epigenetic studies are commonly conducted on DNA from tissue samples. However, tissues are ensembles of cells that may each have their own epigenetic profile, and therefore inter-individual cellular heterogeneity may compromise these studies. Here, we explore the potential for such confounding on DNA methylation measurement outcomes when using DNA from whole blood. DNA methylation was measured using pyrosequencing-based methodology in whole blood (n = 50-179) and in two white blood cell fractions (n = 20), isolated using density gradient centrifugation, in four CGIs (CpG Islands) located in genes HHEX (10 CpG sites assayed), KCNJ11 (8 CpGs), KCNQ1 (4 CpGs) and PM20D1 (7 CpGs). Cellular heterogeneity (variation in proportional white blood cell counts of neutrophils, lymphocytes, monocytes, eosinophils and basophils, counted by an automated cell counter) explained up to 40% (p<0.0001) of the inter-individual variation in whole blood DNA methylation levels in the HHEX CGI, but not a significant proportion of the variation in the other three CGIs tested. DNA methylation levels in the two cell fractions, polymorphonuclear and mononuclear cells, differed significantly in the HHEX CGI; specifically the average absolute difference ranged between 3.4-15.7 percentage points per CpG site. In the other three CGIs tested, methylation levels in the two fractions did not differ significantly, and/or the difference was more moderate. In the examined CGIs, methylation levels were highly correlated between cell fractions. In summary, our analysis detects region-specific differential DNA methylation between white blood cell subtypes, which can confound the outcome of whole blood DNA methylation measurements. Finally, by demonstrating the high correlation between methylation levels in cell fractions, our results suggest a possibility to use a proportional number of a single white blood cell type to correct for this confounding effect in analyses

Prevalence of heart failure in the elderly and future projections: the AGES-Reykjavík study.

To access publisher's full text version of this article click on the hyperlink belowTo assess the prevalence of heart failure (HF) in a randomly selected study population of elderly individuals representing the general population of Iceland. Furthermore, to project the number of individuals likely to have HF in the future.Baseline characteristics and clinical data from 5706 individuals who participated in the population based AGES-Reykjavik Study and gave their informed consent were used. Their age range was 66-98 years (mean age 77.0 ± 5.9 years), 57.6% were females. HF-diagnoses were established by review of hospital records and adjudicated according to prespecified criteria. Data from the 'Statistics Iceland' institution on the current size, age and sex distribution of the population and its prediction into the sixth decade were also used.The prevalence of HF was 3.6% in the sexes combined, but higher in men (5.1%) than women (2.7%) (p < .001). The prevalence of HF per age groups ≤69, 70-74, 75-79, 80-84 and ≥85 years was 1.7%, 1.5%, 3.7%, 5.2% and 7.2%, respectively. The number of individuals ≥70 years with HF will increase considerably in the future. Thus, a calculation based on the projected age distribution and increase in the number of elderly ≥70 years in the coming decades, demonstrated that the number of patients with HF will have increased 2.3-fold by the year 2040 and tripled by the year 2060.This study, in a cohort of elderly participants representative of the general population in a Nordic country, predicts that HF will be a major and increasing health problem in the coming decades.National Institute of Health National Institute of Aging Intramural Research Program Hjartavernd (The Icelandic Heart Association) Althingi (The Icelandic Parliament

Correlation between DNA methylation in mononuclear and polymorphonuclear cells.

<p>Comparison of DNA methylation levels measured in two cell fractions, mononuclear cells (MNCs) and polymorphonuclear cells (PMNCs). Percent methylation in PMNCs (y-axis) is plotted against percent methylation in MNCs (x-axis). Each dot represents the two measurements for a single CpG per individual. The Spearman ρ for correlation between measurements in MNCs and PMNCs for each CGI is shown in the legend.</p

Characteristics of individuals included in the study^*.

*<p>Abbreviations; WB:Whole blood (i.e., population studied for DNA methylation in whole blood), BCF: Blood cell fraction (i.e., population studied for DNA methylation in blood cell fractions), NE: Neutrophils, LY: Lymphocytes, MO: Monocytes, EO: Eosinophils, BA: Basophils.</p