Carotid Endarterectomy in Older Women and Men in the United States: Trends in Ethnic Disparities

Trends in utilization of carotid endarterectomy (CEA) among elderly ethnic minorities have received little attention. Data from the U.S. Centers for Medicare and Medicaid Services were examined for the years 1990 through 2000. In women and men, the rate of CEA per 100,000 non-HMO beneficiaries aged ≥65 years increased in African Americans and in European Americans between 1990 and 1995, with only small changes thereafter. Between 1990 and 2000, the ratio of rates in European Americans to those in African Americans have decreased slightly, i.e., in women from 2.63 in 1990 to 2.24 (15%) in 2000 and in men from 3.94 to 3.39 (14%). Large ethnic differences in utilization of CEA persist in the elderly requiring further evaluation.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2569305

High-density Lipoprotein Cholesterol, Cognitive Function and Mortality in a U.S. National Cohort

Low levels of both high density lipoprotein cholesterol (HDL) and cognitive function are associated with increased mortality risk. HDL plays an important role in brain metabolism. We test the hypotheses that the relative protective effect of high HDL level as related to mortality is greater in persons with impaired cognitive function than in others. Data were analyzed from a longitudinal mortality follow-up study of 4911 American men and women aged 60 years and over examined in 1988-1994 followed an average 8.5 yr. Measurements at baseline included HDL, a short index of cognitive function (SICF), socio-demographics, health status, and self-reported leisure-time physical activity. In proportional hazards regression analysis, no significant interaction of HDL with cognitive function was found (p = 0.08); there was a significant age-SICF interaction. After stratifying by age and adjusting for confounding by multiple variables, independent associations of HDL and SICF score with survival were strongest among the oldest persons. Consistent with its association with HDL, cognitive function and survival, controlling in addition for physical activity reduced the associations. In a nationwide cohort of older Americans, analyses demonstrated a lower risk of death independent of confounders among those high HDL and SICF scores, strongest among the oldest persons

Population Surveillance of Dementia Mortality

Geographic and temporal variation in occurrence of dementia within the US has received little attention despite its importance for generation of new etiologic hypotheses and health services research. We examine methodological problems in the use of vital statistics data for assessing variation over time, among states and within states in the US. We analyzed the US multiple cause of death files for 2005–2006 and 1999–2000 US deaths with Alzheimer’s Disease (International Classification of Disease 10th revision code G30) and other dementias (codes F01, F02, R54) coded as underlying or contributing cause of death based on the death certificate. Age-adjusted death rates were computed by year, state or county for persons aged 65 years and over. In 2005–2006 combined, 555,904 total deaths occurred with any dementia type (212,386 for Alzheimer’s disease) coded as underlying or contributing cause. Among the states, age-adjusted rates per 100,000 per year varied by two fold ranging from 458 in New York to 921 in Oregon. Similar geographic patterns were seen for Alzheimer’s disease. However, between 1999–2000 and 2005–2006 the US death rate for all dementia increased only from 559 to 695 (24%) while that for Alzheimer’s disease doubled from 135 to 266. Use of specific (G30, F01) versus non-specific diagnoses (F02, R54) varied among states and over time, explaining most of the temporal increase in rate of Alzheimer’s disease. Further research is needed to assess artifacts of diagnosis, certification or coding, utilization of health services, versus biological variation as possible causes of temporal and geographic variation to enhance utility of mortality data for dementia monitoring and research

Neuroprotection and Neurodegeneration in Alzheimer's Disease: Role of Cardiovascular Disease Risk Factors, Implications for Dementia Rates, and Prevention with Aerobic Exercise in African Americans

Prevalence of Alzheimer's disease (AD) will reach epidemic proportions in the United States and worldwide in the coming decades, and with substantially higher rates in African Americans (AAs) than in Whites. Older age, family history, low levels of education, and ɛ4 allele of the apolipoprotein E (APOE) gene are recognized risk factors for the neurodegeneration in AD and related disorders. In AAs, the contributions of APOE gene to AD risk continue to engender a considerable debate. In addition to the established role of cardiovascular disease (CVD) risk in vascular dementia, it is now believed that CVD risk and its endophenotype may directly comediate AD phenotype. Given the pleiotropic effects of APOE on CVD and AD risks, the higher rates of CVD risks in AAs than in Whites, it is likely that CVD risks contribute to the disproportionately higher rates of AD in AAs. Though the advantageous effects of aerobic exercise on cognition is increasingly recognized, this evidence is hardly definitive, and data on AAs is lacking. In this paper, we will discuss the roles of CVD risk factors in the development of AD and related dementias, the susceptibility of these risk factors to physiologic adaptation, and fitness-related improvements in cognitive function. Its relevance to AD prevention in AAs is emphasized

Smoking, Cognitive Function and Mortality in a U.S. National Cohort Study

Previous studies report that low levels cognitive function and history of smoking are associated with increased mortality risk. Elderly smokers may have increased risk of dementia, but risk in former smokers is unclear. We tested the hypotheses that the harmful effect of impaired cognitive function as related to mortality is greater in persons smoking at baseline than in others. Further, we used serum cotinine levels to assess recall bias of smoking history by cognitive function level. Data were analyzed from a longitudinal mortality follow-up study of 4,916 American men and women aged 60 years and over, examined in 1988–1994 with complete data followed an average 8.5 years. Measurements at baseline included smoking history, a short index of cognitive function (SICF), serum cotinine and socio-demographics. Death during follow-up occurred in 1,919 persons. In proportional hazards regression analysis, a significant interaction of current smoking with cognitive function was not found; but there was a significant age-smoking interaction. After adjusting for confounding by age or multiple variables, current smoking associated with over 2-fold increased mortality (hazards ratio and 95% confidence limits current versus never smoking 2.13, 1.75–2.59) and SICF with 32% reduction in mortality; top versus bottom SICF stratum 0.68, 0.53–0.88). Serum cotinine data revealed substantial recall bias of smoking history in persons with cognitive impairment. However analyses correcting for this bias did not alter the main conclusions: In a nationwide cohort of older Americans, analyses demonstrated a lower risk of death independent of confounders among those with high SICF scores and never smokers, without a significant interaction of the two

Ischaemic strokes in patients with pulmonary arteriovenous malformations and hereditary hemorrhagic telangiectasia: associations with iron deficiency and platelets.

<div><p>Background</p><p>Pulmonary first pass filtration of particles marginally exceeding ∼7 µm (the size of a red blood cell) is used routinely in diagnostics, and allows cellular aggregates forming or entering the circulation in the preceding cardiac cycle to lodge safely in pulmonary capillaries/arterioles. Pulmonary arteriovenous malformations compromise capillary bed filtration, and are commonly associated with ischaemic stroke. Cohorts with CT-scan evident malformations associated with the highest contrast echocardiographic shunt grades are known to be at higher stroke risk. Our goal was to identify within this broad grouping, which patients were at higher risk of stroke.</p><p>Methodology</p><p>497 consecutive patients with CT-proven pulmonary arteriovenous malformations due to hereditary haemorrhagic telangiectasia were studied. Relationships with radiologically-confirmed clinical ischaemic stroke were examined using logistic regression, receiver operating characteristic analyses, and platelet studies.</p><p>Principal Findings</p><p>Sixty-one individuals (12.3%) had acute, non-iatrogenic ischaemic clinical strokes at a median age of 52 (IQR 41–63) years. In crude and age-adjusted logistic regression, stroke risk was associated not with venous thromboemboli or conventional neurovascular risk factors, but with low serum iron (adjusted odds ratio 0.96 [95% confidence intervals 0.92, 1.00]), and more weakly with low oxygen saturations reflecting a larger right-to-left shunt (adjusted OR 0.96 [0.92, 1.01]). For the same pulmonary arteriovenous malformations, the stroke risk would approximately double with serum iron 6 µmol/L compared to mid-normal range (7–27 µmol/L). Platelet studies confirmed overlooked data that iron deficiency is associated with exuberant platelet aggregation to serotonin (5HT), correcting following iron treatment. By MANOVA, adjusting for participant and 5HT, iron or ferritin explained 14% of the variance in log-transformed aggregation-rate (p = 0.039/p = 0.021).</p><p>Significance</p><p>These data suggest that patients with compromised pulmonary capillary filtration due to pulmonary arteriovenous malformations are at increased risk of ischaemic stroke if they are iron deficient, and that mechanisms are likely to include enhanced aggregation of circulating platelets.</p></div

UDP-glucose 4, 6-dehydratase Activity Plays an Important Role in Maintaining Cell Wall Integrity and Virulence of Candida albicans

Candida albicans, a human fungal pathogen, undergoes morphogenetic changes that are associated with virulence. We report here that GAL102 in C. albicans encodes a homolog of dTDP-glucose 4,6-dehydratase, an enzyme that affects cell wall properties as well as virulence of many pathogenic bacteria. We found that GAL102 deletion leads to greater sensitivity to antifungal drugs and cell wall destabilizing agents like Calcofluor white and Congo red. The mutant also formed biofilms consisting mainly of hyphal cells that show less turgor. The NMR analysis of cell wall mannans of gal102 deletion strain revealed that a major constituent of mannan is missing and the phosphomannan component known to affect virulence is greatly reduced. We also observed that there was a substantial reduction in the expression of genes involved in biofilm formation but increase in the expression of genes encoding glycosylphosphatidylinositol-anchored proteins in the mutant. These, along with altered mannosylation of cell wall proteins together might be responsible for multiple phenotypes displayed by the mutant. Finally, the mutant was unable to grow in the presence of resident peritoneal macrophages and elicited a weak pro-inflammatory cytokine response in vitro. Similarly, this mutant elicited a poor serum pro-inflammatory cytokine response as judged by IFNγ and TNFα levels and showed reduced virulence in a mouse model of systemic candidiasis. Importantly, an Ala substitution for a conserved Lys residue in the active site motif YXXXK, that abrogates the enzyme activity also showed reduced virulence and increased filamentation similar to the gal102 deletion strain. Since inactivating the enzyme encoded by GAL102 makes the cells sensitive to antifungal drugs and reduces its virulence, it can serve as a potential drug target in combination therapies for C. albicans and related pathogens