Apparent diffusion coefficient in the aging mouse brain: a magnetic resonance imaging study

Novel magnetic resonance imaging sequences have and still continue to play an increasing role in neuroimaging and neuroscience. Among these techniques, diffusion-weighted imaging (DWI) has revolutionized the diagnosis and management of diseases such as stroke, neoplastic disease and inflammation. However, the effects of aging on diffusion are yet to be determined. To establish reference values for future experimental mouse studies we tested the hypothesis that absolute apparent diffusion coefficients (ADC) of the normal brain change with age. A total of 41 healthy mice were examined by T2-weighted imaging and DWI. For each animal ADC frequency histograms (i) of the whole brain were calculated on a voxel-by-voxel basis and region-of-interest (ROI) measurements (ii) performed and related to the animals' age. The mean entire brain ADC of mice <3 months was 0.715(+/-0.016) x 10(-3) mm2/s, no significant difference to mice aged 4 to 5 months (0.736(+/-0.040) x 10(-3) mm2/s) or animals older than 9 months 0.736(+/-0.020) x 10(-3) mm2/s. Mean whole brain ADCs showed a trend towards lower values with aging but both methods (i + ii) did not reveal a significant correlation with age. ROI measurements in predefined areas: 0.723(+/-0.057) x 10(-3) mm2/s in the parietal lobe, 0.659(+/-0.037) x 10(-3) mm2/s in the striatum and 0.679(+/-0.056) x 10(-3) mm2/s in the temporal lobe. With advancing age, we observed minimal diffusion changes in the whole mouse brain as well as in three ROIs by determination of ADCs. According to our data ADCs remain nearly constant during the aging process of the brain with a small but statistically non-significant trend towards a decreased diffusion in older animals.

Effects of an aging vascular model on healthy and diseased hearts

The vitamin D(3) and nicotine (VDN) model is a model of isolated systolic hypertension (ISH) due to arterial calcification raising arterial stiffness and vascular impedance similar to an aged and stiffened arterial tree. We therefore analyzed the impact of this aging model on normal and diseased hearts with myocardial infarction (MI). Wistar rats were treated with VDN (n = 9), subjected to MI by coronary ligation (n = 10), or subjected to a combination of both MI and VDN treatment (VDN/MI, n = 14). A sham-treated group served as control (Ctrl, n = 10). Transthoracic echocardiography was performed every 2 wk, whereas invasive indexes were obtained at week 8 before death. Calcium, collagen, and protein contents were measured in the heart and the aorta. Systolic blood pressure, pulse pressure, thoracic aortic calcium, and end-systolic elastance as an index of myocardial contractility were highest in the aging model group compared with MI and Ctrl groups (P(VDN) < 0.05, 2-way ANOVA). Left ventricular wall stress and brain natriuretic peptide (P(VDNxMI) = not significant) were highest, while ejection fraction, stroke volume, and cardiac output were lowest in the combined group versus all other groups (P(VDNxMI) < 0.05). The combination of ISH due to this aging model and MI demonstrates significant alterations in cardiac function. This model mimics several clinical phenomena of cardiovascular aging and may thus serve to further study novel therapies.

Experimental study of physical aging effects on properties of EPON 862-DETDA

Epoxies find variety of applications and during these applications they get exposed to different conditions like elevated temperatures, hydrothermal, chemical, etc. It has been observed that properties of epoxies do get affected substantially if exposed to these conditions for extended period of time and because of the variety of applications, researchers found it necessary to study their effects on the thermal, mechanical, physical and chemical properties. However in this report the focus is on studying effects of physical aging on mechanical properties of EPON 862 with DETDA as its curing agent, where physical aging is aging is the condition which occurs due to exposure to elevated temperatures. A fair amount of computational work has been performed on EPON 862- DETDA to study the effects of physical aging, however very little known work has been done experimentally to study these effects. Young’s modulus, hardness, failure strength, strain to failure, density and glass transition are the properties which have been obtained using various experimental methods - tensile testing, nanoindentation and differential scanning calorimetry. Experimental work on other epoxies have shown no increase or very slight increase in the Young’s modulus and hardness with increased aging time, also decrease in failure strength and strain to failure and through this work on EPON 862- DETDA we can observe similar trends.

Biochemical typing of pathological prion protein in aging cattle with BSE

BACKGROUND: The broad enforcement of active surveillance for bovine spongiform encephalopathy (BSE) in 2000 led to the discovery of previously unnoticed, atypical BSE phenotypes in aged cattle that differed from classical BSE (C-type) in biochemical properties of the pathological prion protein. Depending on the molecular mass and the degree of glycosylation of its proteinase K resistant core fragment (PrPres), mainly determined in samples derived from the medulla oblongata, these atypical cases are currently classified into low (L)-type or high (H)-type BSE. In the present study we address the question to what extent such atypical BSE cases are part of the BSE epidemic in Switzerland. RESULTS: To this end we analyzed the biochemical PrPres type by Western blot in a total of 33 BSE cases in cattle with a minimum age of eight years, targeting up to ten different brain regions. Our work confirmed H-type BSE in a zebu but classified all other cases as C-type BSE; indicating a very low incidence of H- and L-type BSE in Switzerland. It was documented for the first time that the biochemical PrPres type was consistent across different brain regions of aging animals with C-type and H-type BSE, i.e. independent of the neuroanatomical structure investigated. CONCLUSION: Taken together this study provides further characteristics of the BSE epidemic in Switzerland and generates new baseline data for the definition of C- and H-type BSE phenotypes, thereby underpinning the notion that they indeed represent distinct prion disease entities.

Limited managerial attention and corporate aging

As firms have more assets in place, more of management’s limited attention is focused on managing assets in place rather than developing new growth options. Consequently, as firms grow older, they have fewer growth options and a lower ability to generate new growth options. This simple theory predicts that Tobin’s q falls with age. Further, competition in the product market is expected to slow down the decrease in Tobin’s q because it forces firms to look for alternative sources of rents. Similarly, greater competition in the labor market reduces the decrease in Tobin’s q with age because old firms are in a better position to hire employees that can help with innovation. In contrast, competition in the market for corporate control should accelerate the decline because it forces management to focus more on managing assets in place whose performance is more directly observable than on developing growth options where results may not be observable for some time. We find strong support for these predictions in tests using exogenous variation in competition.

Corporate Aging and Takeover Risk

Although growth opportunities fade and profitability declines as firms mature, older firms are no more likely to be acquired than young firms are. This article documents and explains that phenomenon. We argue that, because mature organizations are rationally less flexible, they are more costly to integrate and therefore comparatively unattractive acquisition candidates. The evidence supports this explanation of the negative age dependence of takeover hazard. The evidence also shows that negative exogenous shocks to merger benefits further reduce the takeover hazard of mature firms. We test many alternative explanations and find no evidence that they can explain the hazard decline.

Limited managerial attention and corporate aging

As firms have more assets in place, more of management’s limited attention is focused on managing assets in place rather than developing new growth options. Consequently, as firms grow older, they have fewer growth options and a lower ability to generate new growth options. This simple theory predicts that Tobin’s q falls with age. Further, competition in the product market is expected to slow down the decrease in Tobin’s q because it forces firms to look for alternative sources of rents. Similarly, greater competition in the labor market reduces the decrease in Tobin’s q with age because old firms are in a better position to hire employees that can help with innovation. In contrast, competition in the market for corporate control should accelerate the decline because it forces management to focus more on managing assets in place whose performance is more directly observable than on developing growth options where results may not be observable for some time. We find strong support for these predictions in tests using exogenous variation in competition

Tooth loss and periodontitis in older individuals: results from the Swedish National Study on Aging and Care

BACKGROUND Due to the increasing number of older people, there is a need for studies focused on this population. The aims of the present study are to assess oral and systemic conditions in individuals aged 60 to 95 years with access to dental insurance. METHODS Probing depths (PDs), tooth loss, alveolar bone levels, and systemic health were studied among a representative cohort of older individuals. RESULTS A total of 1,147 individuals in young-old (aged 60 or 67 years), old (aged 72 or 78 years), and old-old (aged ≥81 years) age groups were enrolled, including 200 individuals who were edentulous, in this study. Annual dental care was received by 82% of dentate individuals. Systemic diseases were common (diabetes: 5.8%; cardiovascular diseases: 20.7%; obesity: 71.2%; elevated C-reactive protein [CRP]: 98.4%). Serum CRP values were unrelated to periodontal conditions. Rates of periodontitis, defined as ≥30% of sites with a distance from cemento-enamel junction to bone of ≥5 mm, were 11.2% in women in the young-old age group and 44.9% in men in the old-old age group. Individuals in older age groups had a higher likelihood of periodontitis defined by bone loss and cutoff levels of PD ≥5 mm (odds ratio: 1.8; 95% confidence interval: 1.2 to 2.5; P <0.01). A total of 7% of individuals in the old-old age group had ≥20 teeth and no periodontitis. Systemic diseases, dental use, or smoking were not explanatory, whereas age and sex were explanatory for periodontitis. CONCLUSIONS The prevalence of periodontitis increased with age. Sex seems to be the dominant explanatory factor for periodontitis in older individuals. Despite frequent dental visits, overall oral health in the oldest age cohort was poor.

Frailty and risk for heart failure in older adults: the health, aging, and body composition study

OBJECTIVE The aim of this study was to assess the association between frailty and risk for heart failure (HF) in older adults. BACKGROUND Frailty is common in the elderly and is associated with adverse health outcomes. Impact of frailty on HF risk is not known. METHODS We assessed the association between frailty, using the Health ABC Short Physical Performance Battery (HABC Battery) and the Gill index, and incident HF in 2825 participants aged 70 to 79 years. RESULTS Mean age of participants was 74 ± 3 years; 48% were men and 59% were white. During a median follow up of 11.4 (7.1-11.7) years, 466 participants developed HF. Compared to non-frail participants, moderate (HR 1.36, 95% CI 1.08-1.71) and severe frailty (HR 1.88, 95% CI 1.02-3.47) by Gill index was associated with a higher risk for HF. HABC Battery score was linearly associated with HF risk after adjusting for the Health ABC HF Model (HR 1.24, 95% CI 1.13-1.36 per SD decrease in score) and remained significant when controlled for death as a competing risk (HR 1.30; 95% CI 1.00-1.55). Results were comparable across age, sex, and race, and in sub-groups based on diabetes mellitus or cardiovascular disease at baseline. Addition of HABC Battery scores to the Health ABC HF Risk Model improved discrimination (change in C-index, 0.014; 95% CI 0.018-0.010) and appropriately reclassified 13.4% (net-reclassification-improvement 0.073, 95% CI 0.021-0.125; P = .006) of participants (8.3% who developed HF and 5.1% who did not). CONCLUSIONS Frailty is independently associated with risk of HF in older adults.

Electrocardiographic PR interval and adverse outcomes in older adults: the Health, Aging, and Body Composition study

BACKGROUND The electrocardiographic PR interval increases with aging, differs by race, and is associated with atrial fibrillation (AF), pacemaker implantation, and all-cause mortality. We sought to determine the associations between PR interval and heart failure, AF, and mortality in a biracial cohort of older adults. METHODS AND RESULTS The Health, Aging, and Body Composition (Health ABC) Study is a prospective, biracial cohort. We used multivariable Cox proportional hazards models to examine PR interval (hazard ratios expressed per SD increase) and 10-year risks of heart failure, AF, and all-cause mortality. Multivariable models included demographic, anthropometric, and clinical variables in addition to established cardiovascular risk factors. We examined 2722 Health ABC participants (aged 74±3 years, 51.9% women, and 41% black). We did not identify significant effect modification by race for the outcomes studied. After multivariable adjustment, every SD increase (29 ms) in PR interval was associated with a 13% greater 10-year risk of heart failure (95% confidence interval, 1.02-1.25) and a 13% increased risk of incident AF (95% confidence interval, 1.04-1.23). PR interval >200 ms was associated with a 46% increased risk of incident heart failure (95% confidence interval, 1.11-1.93). PR interval was not associated with increased all-cause mortality. CONCLUSIONS We identified significant relationships of PR interval to heart failure and AF in older adults. Our findings extend prior investigations by examining PR interval and associations with adverse outcomes in a biracial cohort of older men and women.

Sex differences in the prevalence and clinical outcomes of subclinical peripheral artery disease in the Health, Aging, and Body Composition (Health ABC) study

The objective of the study was to determine if there are sex-based differences in the prevalence and clinical outcomes of subclinical peripheral artery disease (PAD). We evaluated the sex-specific associations of ankle-brachial index (ABI) with clinical cardiovascular disease outcomes in 2797 participants without prevalent clinical PAD and with a baseline ABI measurement in the Health, Aging, and Body Composition study. The mean age was 74 years, 40% were black, and 52% were women. Median follow-up was 9.37 years. Women had a similar prevalence of ABI < 0.9 (12% women versus 11% men; P = 0.44), but a higher prevalence of ABI 0.9-1.0 (15% versus 10%, respectively; P < 0.001). In a fully adjusted model, ABI < 0.9 was significantly associated with higher coronary heart disease (CHD) mortality, incident clinical PAD and incident myocardial infarction in both women and men. ABI < 0.9 was significantly associated with incident stroke only in women. ABI 0.9-1.0 was significantly associated with CHD death in both women (hazard ratio 4.84, 1.53-15.31) and men (3.49, 1.39-8.72). However, ABI 0.9-1.0 was significantly associated with incident clinical PAD (3.33, 1.44-7.70) and incident stroke (2.45, 1.38-4.35) only in women. Subclinical PAD was strongly associated with adverse CV events in both women and men, but women had a higher prevalence of subclinical PAD.