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

Percent DNA methylation in mononuclear and polymorphonuclear cells.

<p>Percent DNA methylation (y-axis) in mononuclear and polymorphonuclear cells (MNCs and PMNCs) per CpG site (x-axis) in four CGIs located in the <i>HHEX</i>, <i>KCNJ11</i>, <i>KCNQ1</i> and <i>PM20D1</i> genes respectively (n = 20 each). Data for each CGI are depicted in a separate boxplot where measurements for MNCs are shown in red and for PMNCs in blue. The dotted lines separating the boxes indicate that at each CpG site a pair of data are being compared (i.e., for MNCs and PMNCs). Significantly (p<0.01) differentially methylated CpG sites (MNCs versus PMNCs DNA methylation) are indicated with an asterisk.</p

PC-MRI for quantification of total CBF.

<p>(a) A PC-MRI scan for measuring mean tCBF was prescribed on a PC-MRI sagittal localizer image perpendicular to the carotid arteries at the level of the mid basilar artery. (b) A representative phase image demonstrating the right and left internal carotid arteries (R.ICA and L.ICA) together with the basilar artery (BA).</p

Percent DNA methylation in whole blood samples.

<p>Percent DNA methylation (y-axis) in whole blood DNA per CpG site (x-axis) in four CGIs located in the <i>HHEX</i> (n = 169), <i>KCNJ11</i> (n = 54), <i>KCNQ1</i> (n = 49) and <i>PM20D1</i> (n = 59) genes respectively. Data for each CGI are depicted in a separate boxplot. Below each boxplot is a gene-map which roughly indicates the position of the analyzed CpG sites (adapted from the UCSC genome browser) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046705#pone.0046705-Kent1" target="_blank">[12]</a>. Genes are depicted in blue, the exons as blocks, the introns as thin lines connecting the blocks, and the 5′ and 3′ untranslated regions as thin blocks at each end. CGIs are shown as green blocks. The genomic position depicted for each CGI is; 10:94,439,661–94,445,388 (chromosome:first base-last base) for the <i>HHEX</i> CGI, chr11:17,363,372–17,366,783 for the <i>KCNJ11</i> CGI, chr11:2,422,797–2,826,916 for the <i>KCNQ1</i> CGI and chr1:204,063,776–204,085,881 for the <i>PM20D1</i> CGI. The gene map for <i>KCNQ1</i> includes the <i>KCNQ1OT1</i> (<i>KCNQ1</i> overlapping transcript 1) gene, which appears as a large exon roughly in the middle of the map. Arrows indicate the direction of transcription and the position of the transcription start site.</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

Comparison of CBF values at rest and activation.

<p>(a) Average CBF maps of the entire study sample (n = 17) of the first scan at rest (Rest 1), rescan at rest (Rest 2) and at activation by bilateral finger-tapping (activation). (b) Comparison of CBF values at rest and activation by finger-tapping on a voxel level showed significantly higher perfusion during activation in the motor and somatosensory regions at threshold p≤0.01.</p

Representative CBF maps of one study participant.

<p>Representative CBF maps of an 80 year old male participant with whole brain CBF 47.6 and 49.5 ml/100g/min for the first and second scan at rest respectively. (a) First row corresponds to first scan at rest and (b) second row to rescan at rest.</p

Agreement between scans at rest for whole brain CBF.

<p>Bland-Altman plot demonstrating the agreement between the first and second scan at rest for whole brain CBF. Solid mid and upper-lower lines are the mean bias and limits of agreement (1.96 standard deviation), respectively. Y-axis displays mean difference between first and second scan and x-axis the average CBF of the first and second scan.</p

Image_1_N-Terminal pro-Brain Natriuretic Peptide and Associations With Brain Magnetic Resonance Imaging (MRI) Features in Middle Age: The CARDIA Brain MRI Study.tiff

Objective<p>As part of research on the heart–brain axis, we investigated the association of N-terminal pro-brain natriuretic peptide (NT-proBNP) with brain structure and function in a community-based cohort of middle-aged adults from the Brain Magnetic Resonance Imaging sub-study of the Coronary Artery Risk Development in Young Adults (CARDIA) Study.</p>Approach and results<p>In a cohort of 634 community-dwelling adults with a mean (range) age of 50.4 (46–52) years, we examined the cross-sectional association of NT-proBNP to total, gray (GM) and white matter (WM) volumes, abnormal WM load and WM integrity, and to cognitive function tests [the Digit Symbol Substitution Test (DSST), the Stroop test, and the Rey Auditory–Verbal Learning Test]. These associations were examined using linear regression models adjusted for demographic and cardiovascular risk factors and cardiac output. Higher NT-proBNP concentration was significantly associated with smaller GM volume (β = −3.44; 95% CI = −5.32, −0.53; p = 0.003), even after additionally adjusting for cardiac output (β = −2.93; 95% CI = −5.32, −0.53; p = 0.017). Higher NT-proBNP levels were also associated with lower DSST scores. NT-proBNP was not related to WM volume, WM integrity, or abnormal WM load.</p>Conclusion<p>In this middle-aged cohort, subclinical levels of NT-proBNP were related to brain function and specifically to GM and not WM measures, extending similar findings in older cohorts. Further research is warranted into biomarkers of cardiac dysfunction as a target for early markers of a brain at risk.</p

Vascular Factors and Multiple Measures of Early Brain Health: CARDIA Brain MRI Study

<div><p>Objective</p><p>To identify early changes in brain structure and function that are associated with cardiovascular risk factors (CVRF).</p><p>Design</p><p>Cross-sectional brain Magnetic Resonance I (MRI) study.</p><p>Setting</p><p>Community based cohort in three U.S. sites.</p><p>Participants</p><p>A Caucasian and African-American sub-sample (n= 680; mean age 50.3 yrs) attending the 25 year follow-up exam of the Coronary Artery Risk Development in Young Adults Study.</p><p>Primary and Secondary Outcomes</p><p>3T brain MR images processed for quantitative estimates of: total brain (TBV) and abnormal white matter (AWM) volume; white matter fractional anisotropy (WM-FA); and gray matter cerebral blood flow (GM-CBF). Total intracranial volume is TBV plus cerebral spinal fluid (TICV). A Global Cognitive Function (GCF) score was derived from tests of speed, memory and executive function.</p><p>Results</p><p>Adjusting for TICV and demographic factors, current smoking was significantly associated with lower GM-CBF and TBV, and more AWM (all <0.05); SA with lower GM-CBF, WM-FA and TBV (p=0.01); increasing BMI with decreasing GM-CBF (p<0003); hypertension with lower GM-CBF, WM-FA, and TBV and higher AWM (all <0.05); and diabetes with lower TBV (p=0.007). The GCS was lower as TBV decreased, AWM increased, and WM-FA (all p<0.01).</p><p>Conclusion</p><p>In middle age adults, CVRF are associated with brain health, reflected in MRI measures of structure and perfusion, and cognitive functioning. These findings suggest markers of mid-life cardiovascular and brain health should be considered as indication for early intervention and future risk of late-life cerebrovascular disease and dementia.</p></div