Macrophages come to mind as keys to cognitive decline

Cognitive impairment, an underappreciated consequence of hypertension, is linked to cerebral arteriolar disease through poorly defined mechanisms. A study by Faraco et al. in this issue of the JCI points to perturbations of neurovascular unit coupling caused by perivascular macrophages (PVMs) as a cause of hypertension-related cognitive impairment. Angiotensin II (Ang II) was shown to activate PVMs, causing them to produce superoxide and thereby alter the proper functioning of the adjacent arterioles. Faraco and colleagues also show that disruption of the blood-brain barrier occurs in hypertension, allowing circulating Ang II to access PVMs. This study provides important new insight into the role of inflammatory cells in the genesis of vascular dementia

Silica nanowires templated by amyloid-like fibrils

Many peptides self-assemble to form amyloid fibrils. We previously explored the sequence propensity to form amyloid using variants of a designed peptide with sequence KFFEAAAKKFFE. These variant peptides form highly stable amyloid fibrils with varied lateral assembly and are ideal to template further assembly of non-proteinaceous material. Herein, we show that the fibrils formed by peptide variants can be coated with a layer of silica to produce silica nanowires using tetraethyl-orthosilicate. The resulting nanowires were characterized using electron microscopy (TEM), X-ray fiber diffraction, FTIR and cross-section EM to reveal a nanostructure with peptidic core. Lysine residues play a role in templating the formation of silica on the fibril surface and, using this library of peptides, we have explored the contributions of lysine as well as arginine to silica templating, and find that sequence plays an important role in determining the physical nature and structure of the resulting nanowires

Can an evolutionary perspective shed light on maternal abuse of children?

Although the theory of evolution lies at the heart of contemporary biology, its influence on the study of child psychology and psychiatry has been limited. In earlier work we have argued that evolutionary thinking has much of value for clinicians. Here, we explore the possible significance of evolutionary theory for understanding child abuse by mothers, particularly neglect, emotional abuse and physical abuse. We draw on the research of anthropologists, primatologists and evolutionary theorists to make predictions about the environmental circumstances under which one would expect such abuse to be more prevalent. We discuss how in modern, Western cultures there is less understanding of the circumstances that may influence, even predispose, a mother to limit her emotional and material commitment to an infant or child. We use four short vignettes of clinical cases and one longer case description to illustrate the insights offered to clinicians by an evolutionary approach. We see our work both as contributing to greater understanding of these matters and as facilitating more compassionate models of care and intervention for women in such circumstances

Smoking and alcohol consumption in relation to cognitive performance at middle age.

In the elderly, cigarette smoking has been related to reduced cognitive performance and moderate alcohol consumption to increased cognitive performance. It is not clear whether these associations also exist in middle age. The authors examined these relations in a population-based cohort study of 1,927 randomly selected, predominantly middle-aged subjects aged 45-70 years at the time of cognitive testing and living in the Netherlands. From 1995 until 2000, an extensive cognitive battery was administered, and compound scores were calculated. Risk factors had been assessed approximately 5 years previously. Multiple linear regression analyses (in which one unit of the cognitive score = one standard deviation) showed that, after the authors adjusted for age, sex, education, alcohol consumption, and cardiovascular risk factors, current smokers had reduced psychomotor speed (beta = -0.159, 95% confidence interval: -0.071, -0.244; p = 0.0003) and reduced cognitive flexibility (beta = -0.133, 95% confidence interval: -0.035,-0.230; p = 0.008) compared with never smokers. This effect was similar to that of being approximately 4 years older. Alcohol consumption was related to increased speed and better flexibility, especially among women who drank 1-4 alcoholic beverages a day. In conclusion, among middle-aged subjects, current smoking was inversely and alcohol consumption positively related to psychomotor speed and cognitive flexibility. This finding suggests that actions to prevent cognitive decline can be taken in middle age

Trends in body weight and diabetes in forty years in Iceland

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/OpenOBJECTIVE: Obesity and diabetes are increasing problems worldwide. Therefore, new data on these issues are of importance. Here, we publish data on body mass index (BMI) and prevalence of diabetes of type 2 in Iceland. MATERIAL AND METHODS: Mean BMI (kg/m2), prevalence of diabetes type 2 and obesity in people aged 45-64 years were evaluated from 1967 to 2007. Data on type 2 diabetes was based on four population Icelandic Heart Association studies (newest the REFINE (The Risk Evaluation For INfarct Estimates) Reykjavik study from 2006) with total of 17.757 individuals. Data on BMI was in addition based on three further studies, total 20.519 individuals. The same estimates were then performed for 25-84 year old people in the years 2004-2007. These were based on data from the REFINE Reykjavik study 2.410 individuals and the AGES Reykjavik study 3.027 individuals and. RESULTS: In the years 1967-2007 mean BMI increased by 2 units in both genders (45-64 year) and the prevalence of type 2 diabetes doubled in men, while the increase in women was 50%. In the years 2004-2007 the prevalence of diabetes type 2 in 25-84 year old people was 6% in men and 3% in women and the prevalence of obesity was 23% in men and 21% in women. CONCLUSIONS: Mean BMI is increasing in Iceland, especially after 1980. Prevalence of diabetes coincides with increasing body mass index.Tilgangur: Offita og sykursýki eru vaxandi vandamál og mikilvægt að nýjar upplýsingar um þessa þætti liggi fyrir. Hér er greint frá þróun líkamsþyngdarstuðuls og sykursýki af tegund 2 á Íslandi. Efniviður og aðferðir: Meðallíkamsþyngdar-stuðull (kg/m2), algengi sykursýki af tegund 2 og algengi offitu hjá 45-64 ára voru könnuð frá 1967 til 2007. Algengi sykursýki byggist á fjórum rannsóknum Hjartaverndar: Áfanga I-V í Hóprannsókn 1967-1991, Afkomendarannsókn 1997-2001, Rannsókn á ungu fólki 2001-2003 og Áhættuþáttakönnun frá 2006-2007, samtals 17.757 manns. Könnun á líkamsþyngdarstuðli byggist að auki á gögnum úr Monica-rannsókninni á Íslandi frá 1983, 1988 og 1993, heildarfjöldi 20.519. Sömu þættir voru einnig kannaðir fyrir 25-84 ára frá 2004 til 2007. Þá var notast við Áhættuþáttakönnun Hjartaverndar, 2410 manns og Öldrunarrannsókn Hjartaverndar, 3027 manns. Niðurstöður: Meðallíkamsþyngdarstuðull jókst um tvær einingar hjá báðum kynjum (45-64 ára) og algengi sykursýki af tegund 2 tvöfaldaðist hjá körlum og jókst um 50% hjá konunum á árunum 1967-2007. Algengi sykursýki af tegund 2 hjá 25-84 ára, á árunum 2004-2007 var 6% hjá körlum og 3% hjá konum. Algengi offitu var 23% hjá körlum en 21% hjá konum. Ályktanir: Meðallíkamsþyngdarstuðull hefur aukist undanfarna áratugi, einkum eftir 1980. Sykursýki eykst í hlutfalli við vaxandi ofþyngd

Migraine and vascular disease biomarkers: A population-based case-control study.

Background The underpinnings of the migraine-stroke association remain uncertain, but endothelial activation is a potential mechanism. We evaluated the association of migraine and vascular disease biomarkers in a community-based population. Methods Participants (300 women, 117 men) were recruited as a part of the Dutch CAMERA 1 (Cerebral Abnormalities in Migraine, an Epidemiologic Risk Analysis) study. Participants were aged 30-60 (mean 48) years, 155 migraine had with aura (MA), 128 migraine without aura (MO), and 134 were controls with no severe headaches. Plasma concentrations of fibrinogen, Factor II, D-dimer, high sensitivity C-reactive protein (hs-CRP), and von Willebrand factor antigen were compared between groups, also stratifying by sex. Results Fibrinogen and hs-CRP were elevated in migraineurs compared to controls. In logistic regression analyses, MO and MA had increased likelihood of elevated fibrinogen, and MA had increased likelihood of elevated Factor II and hs-CRP. Fibrinogen and Factor II were associated with MA in women but not men. In the migraine subgroup, the total number of years of aura, but not headache, predicted elevated hs-CRP, and the average number of aura, but not headache, attacks predicted all biomarkers but Factor II. Conclusions Elevated vascular biomarkers were associated with migraine, particularly MA, as well as with years of aura and number of aura attacks

Chiral condensates from tau decay: a critical reappraisal

The saturation of QCD chiral sum rules is reanalyzed in view of the new and complete analysis of the ALEPH experimental data on the difference between vector and axial-vector correlators (V-A). Ordinary finite energy sum rules (FESR) exhibit poor saturation up to energies below the tau-lepton mass. A remarkable improvement is achieved by introducing pinched, as well as minimizing polynomial integral kernels. Both methods are used to determine the dimension d=6 and d=8 vacuum condensates in the Operator Product Expansion, with the results: {O}_{6}=-(0.00226 \pm 0.00055) GeV^6, and O_8=-(0.0053 \pm 0.0033) GeV^8 from pinched FESR, and compatible values from the minimizing polynomial FESR. Some higher dimensional condensates are also determined, although we argue against extending the analysis beyond dimension d = 8. The value of the finite remainder of the (V-A) correlator at zero momentum is also redetermined: \Pi (0)= -4 \bar{L}_{10}=0.02579 \pm 0.00023. The stability and precision of the predictions are significantly improved compared to earlier calculations using the old ALEPH data. Finally, the role and limits of applicability of the Operator Product Expansion in this channel are clarified.Comment: Replaced versio

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

The interaction of adiposity with the CRP gene affects CRP levels: age, gene/environment susceptibilty-Reykjavik study

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldOBJECTIVE: Common diseases often have an inflammatory component reflected by associated markers such as serum C-reactive protein (CRP) levels. Circulating CRP levels have also been associated with adipose tissue as well as with specific CRP genotypes. We examined the interaction between measures of body mass index (BMI), waist circumference and fat percent (total fat measured by bioimpedance) with genotypes of the CRP gene in the determination of CRP levels. METHODS: The first 2296 participants (mean age 76+/-6 years, 42% men) in the Age, Gene/Environment Susceptibility-Reykjavik Study, a multidisciplinary epidemiological study to determine risk factors in aging, were genotyped for 10 single nucleotide polymorphisms (SNPs) in the CRP gene. General linear models with age and terms for interaction of CRP genotypes with BMI, waist circumference and percent fat were used to evaluate the association of genotypes to CRP levels (high-sensitivity method, range 0-10 mg l(-1)) in men and women separately. RESULTS: We focused on the SNP rs1205 that represents the allele that captures the strongest effects of the gene on CRP levels. Carriers of the rs1205 G allele had significantly higher CRP levels than noncarriers in a dose-dependent manner. Compared to the AA genotype, the slope of the increase in CRP with increasing BMI (P=0.045) and waist circumference (P=0.014) was different for the G allele carriers and of similar magnitude in both men and women. The rs1205 interactions were not significant for fat mass percent, suggesting a possible association with fat localization. CONCLUSIONS: This study further illuminates the known association between measures of adiposity and CRP levels and is shown to be dependent on variation in the rs1205 SNP of the CRP gene. The correlated increase in CRP levels with adiposity is accentuated by presence of the G allele