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Apolipoprotein-ε4 (APOE-ε4) is a major genetic risk factor for cognitive decline, Alzheimer's disease (AD) and early mortality. An accelerated rate of biological aging could contribute to this increased risk. Here, we determined whether APOE-ε4 status impa

Purpose: We examined the association between patient experience of care and utilization of hormone therapy (HT) in the treatment of non-metastatic hormone-receptor positive (HR+) breast cancer. Methods: Patients newly diagnosed with non-metastatic breast cancer were recruited from 2006 to 2010 for a longitudinal multisite cohort study in New York, NY, Detroit, MI, and Northern California. Of 1,145 patients surveyed, 797 had HR+ tumors eligible for HT and all necessary data. We assessed patient experience 4 to 8 weeks after recruitment using 6 subscales of the Interpersonal Processes of Care (IPC) survey: compassion, discrimination, and hurriedness in communication, as well as concern elicitation, result explanation, and patient-centered decision-making. Subscales ranged from 1 to 5 where higher values indicated better experiences. HT for 5 years is standard care for HR+ breast cancer so utilization was defined as time from diagnosis to HT initiation and time from HT initiation to early discontinuation before 5 years as calculated from follow-up survey responses. We evaluated the relationship between patient experience and utilization using Cox proportional hazard models, controlling for education, income, insurance, marital status, social support, site of care, age at diagnosis, stage, grade, tumor size, Charlson comorbidity index, and chemotherapy. Results: Median age at diagnosis was 59 years (interquartile range 51-66) with the majority diagnosed at clinical stage 1 (54%) and with low or moderate grade disease (78%). Less hurried communication was associated with increased probability of HT initiation (Hazards Ratio (HR) 1.15; 95% Confidence Interval (CI) 1.03, 1.30; p = 0.018). Conversely, more patient-centered decision-making was associated with increased probability of early discontinuation (HR 1.29; CI, 1.03, 1.63; p = 0.028). All other associations were null. Conclusion: While unhurried communication was associated with initiation of hormone therapy, patient-centered decision-making was associated with early discontinuation. Different aspects of patient experience may have vastly different relationships with patient utilization of health services. Actionable assessments of patient experience may require measurement along multiple dimensions. [ABSTRACT FROM AUTHOR]

It is assumed that total and visceral adiposity increase cardiovascular disease (CVD) risk among breast cancer survivors; yet, these associations have not been studied, and could differ from non-cancer populations due to the modifying effects of cancer treatment. METHODS: We studied 2,630 Stage I-III breast cancer patients without pre-existing CVD diagnosed at Kaiser Permanente (2006-2013). We quantified body composition from computed tomography scans taken at breast cancer diagnosis. The main exposures were total and visceral adiposity indices (cm2/m2), examined in tertiles. From ICD codes, we identified non-fatal stroke, coronary artery disease (CAD), and heart failure, and a composite outcome including CVD death (CVD). We estimated hazard ratios (HR) and 95% confidence intervals (CI) adjusting for age, smoking, tumor (stage, grade, and ER/PR and HER2 status) and treatment (chemotherapy and/or radiation) factors, skeletal muscle index (SMI), and body mass index (BMI) residuals. We assessed effect modification via product terms of adiposity with age (>=/<55 years), sarcopenia (SMI>=/<40 cm2/m2) and chemotherapy (yes/no). RESULTS: At diagnosis, mean (SD) age was 55 (11) years and BMI was 28 (6) kg/m2. Over a maximum follow-up of 11 years, 669 CVD events occurred. Independent of BMI and other covariates, women in the highest (v. lowest) tertile of total adiposity had a higher risk of CVD, heart failure, stroke and CAD; HRs (95%CI) were 1.45 (1.15-1.81), 1.78 (1.24-2.57), 1.89 (1.25-2.87), and 1.52 (0.83-2.79), respectively. Results were similar for visceral adiposity, and by age and sarcopenia, but were stronger for women receiving chemotherapy: e.g., the HR (95%CI) for the highest (v. lowest) tertile of total adiposity with CVD risk was 1.76 (1.33-2.33) for women who received chemotherapy versus 0.93 (0.63-1.38) for women who did not, p- interaction = 0.04. CONCLUSIONS: Women who enter a breast cancer diagnosis with greater total and visceral adiposity are at higher risk of subsequent CVD, particularly if they receive chemotherapy. Our results suggest that body composition - independent of BMI and other factors - can identify patients with high CVD risk for additional monitoring, tailored treatment plans and targeting of preventive interventions. [ABSTRACT FROM AUTHOR]

We examined the prospective associations of social isolation and loneliness with incident cardiovascular disease (CVD) among aging nonveteran and veteran women, and effect modification by veteran status. Participants with no history of myocardial infarction (MI), stroke, coronary heart disease (CHD), or coronary heart failure from the Women's Health Initiative Extension Study II self-reported social isolation, loneliness, health behaviors, health status, and veteran status. CVD and CVD subevents were physician adjudicated. Hazard ratios (HR) and 95% confidence intervals (CI) for the Interquartile Range (IQR) in social isolation (IQR = 1) and loneliness (IQR=.33) were calculated using Cox proportional hazard models adjusting for sociodemographic, health behavior, and health status characteristics. Veteran status was tested as an effect modifier. Among 52,442 women (Mean age = 79 ± 6.1; veterans n  = 1023; 89.2% non-Hispanic White), 3579 major CVD events occurred over an average 5.8 follow-up years. Compared to nonveterans, veteran women reported higher levels of social isolation ( p < .01) and loneliness ( p < .01). The CVD HR was 1.07 (95% CI, 1.04-1.10) for the IQR in social isolation and 1.03 (95% CI, 1.10-1.06) for the IQR in loneliness. The HR for the IQR in both social isolation and loneliness was 1.10 (95% CI, 1.05-1.15). Social isolation was associated with CHD (HR = 1.12; 95% CI, 1.03-1.21). The CHD HR for the IQR in social isolation was 1.12 (95% CI, 1.03-1.21). Associations did not differ by veteran status (all p -interactions > 0.08). Findings suggest that the adverse associations of social isolation and loneliness with CVD are similar among veteran and nonveteran women.

Recent efforts to chart human brain growth across the lifespan using large-scale MRI data have provided reference standards for human brain development. However, similar models for nonhuman primate (NHP) growth are lacking. The rhesus macaque, a widely used NHP in translational neuroscience due to its similarities in brain anatomy, phylogenetics, cognitive, and social behaviors to humans, serves as an ideal NHP model. This study aimed to create normative growth charts for brain structure across the macaque lifespan, enhancing our understanding of neurodevelopment and aging, and facilitating cross-species translational research. Leveraging data from the PRIMatE Data Exchange (PRIME-DE) and other sources, we aggregated 1,522 MRI scans from 1,024 rhesus macaques. We mapped non-linear developmental trajectories for global and regional brain structural changes in volume, cortical thickness, and surface area over the lifespan. Our findings provided normative charts with centile scores for macaque brain structures and revealed key developmental milestones from prenatal stages to aging, highlighting both species-specific and comparable brain maturation patterns between macaques and humans. The charts offer a valuable resource for future NHP studies, particularly those with small sample sizes. Furthermore, the interactive open resource (https://interspeciesmap.childmind.org) supports cross-species comparisons to advance translational neuroscience research.

Although racial/ethnic disparities in health-care access, treatment, and cancer outcomes are well documented, the impact of racial/ethnic discrimination on cancer survivorship is unclear. We examined associations between quality of life (QoL) and self-reported discrimination among 3,991 women with breast cancer recruited during 2006-2013 from the Pathways Study in the Kaiser Permanente Northern California integrated health-care system, using linear regression models. Overall, 31% of women reported experiencing racial/ethnic discrimination, with differences by race/ethnicity (82% among non-Hispanic Black women vs. 19% among non-Hispanic White women) and nativity (40% among foreign-born Hispanic women vs. 76% among US-born Asian-American women). Experiencing racial/ethnic discrimination was associated with lower QoL in fully adjusted models. The mean QoL score was 119.6 (95% confidence interval (CI): 102.0, 137.1) for women who did not report discrimination, 115.5 (95% CI: 98.0, 133.0) for those who reported some discrimination/less than the median level, and 110.2 (95% CI: 92.7, 127.7) for those who reported more discrimination/greater than or equal to the median level. Discrimination was associated with lower QoL among women who used passive coping strategies or lived in neighborhoods with high neighborhood socioeconomic status, neighborhoods with high levels of segregation, or non-ethnic enclaves. Among breast cancer survivors, clinically meaningful differences in QoL scores were associated with racial/ethnic discrimination. Additional studies are needed to understand potential pathways through which these social factors affect survivorship outcomes., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Research has suggested optimism is associated with healthy aging and exceptional longevity, but most studies were conducted among non-Hispanic White populations. We examined associations of optimism to longevity across racial and ethnic groups and assessed healthy lifestyle as a possible mediating pathway., Methods: Participants from the Women's Health Initiative (N = 159,255) completed a validated measure of optimism and provided other demographic and health data at baseline. We evaluated associations of optimism with increments in lifespan using accelerated failure time models, and with likelihood of exceptional longevity (survival to age ≥90) using Poisson regression models. Causal mediation analysis explored whether lifestyle-related factors mediated optimism-lifespan associations., Results: After covariate adjustment, the highest versus lowest optimism quartile was associated with 5.4% (95% confidence interval [CI] = 4.5, 6.4%) longer lifespan. Within racial and ethnic subgroups, these estimates were 5.1% (95%CI = 4.0, 6.1%) in non-Hispanic White, 7.6% (95%CI = 3.6, 11.7%) in Black, 5.4% (95%CI = -0.1, 11.2%) in Hispanic/Latina, and 1.5% (95% CI = -5.0, 8.5) in Asian women. A high proportion (53%) of the women achieved exceptional longevity. Participants in the highest versus lowest optimism quartile had greater likelihood of achieving exceptional longevity (e.g., full sample risk ratio = 1.1, 95%CI = 1.1, 1.1). Lifestyle mediated 24% of the optimism-lifespan association in the full sample, 25% in non-Hispanic White, 10% in Black, 24% in Hispanic/Latina, and 43% in Asian women., Conclusions: Higher optimism was associated with longer lifespan and a greater likelihood of achieving exceptional longevity overall and across racial and ethnic groups. The contribution of lifestyle to these associations was modest. Optimism may promote health and longevity in diverse racial and ethnic groups. Future research should investigate these associations in less long-lived populations., (© 2022 The American Geriatrics Society.)

Background: In the Women's Health Initiative (WHI) dietary modification (DM) randomised trial, the low-fat dietary intervention reduced deaths from breast cancer (P = 0.02). Extending these findings, secondary analysis examined dietary intervention influence on breast cancer mortality by metabolic syndrome (MS) components., Methods: In total, 48,835 postmenopausal women with no prior breast cancer were randomised to a low-fat dietary intervention or comparison groups. Four MS components were determined at entry in 45,833 participants: (1) high waist circumference, (2) high blood pressure, (3) high cholesterol and (4) diabetes history. Forest plots of hazard ratios (HRs) were generated with P-values for interaction between randomisation groups and MS component score. Primary outcome was death from breast cancer by metabolic syndrome score., Results: HRs and 95% confidence intervals (CI) for dietary intervention influence on death from breast cancer were with no MS components (n = 10,639), HR 1.09, 95% CI 0.63-1.87; with 1-2 MS components (n = 30,948), HR 0.80, 95% CI 0.62-1.02; with 3-4 MS components (n = 4,246), HR 0.31, 95% CI 0.14-0.69 (interaction P = 0.01)., Conclusions: While postmenopausal women with 3-4 MS components were at higher risk of death from breast cancer, those randomised to a low-fat dietary intervention more likely had reduction in this risk., Registry: ClinicalTrials.gov (NCT00000611)., (© 2021. The Author(s), under exclusive licence to Cancer Research UK.)

Background: physical and mental health are important risk factors for cardiovascular disease (CVD) incidence and death among postmenopausal women. The objective of this study was to assess whether changes in physical and mental health were associated with CVD incidence and death., Methods: in the Women's Health Initiative Observational Study, 48,906 women (50-79 years) had complete data at baseline on physical and mental health (assessed with Short Form-36) and key covariates. Changes in self-reported physical and mental health were calculated between baseline and year 3. Incident CVD and death between year 3 and end of the study were verified with medical records., Results: over a median 8.2-year follow-up, 2,319 women developed CVD, and 1,571 women died, including 361 CVD deaths. Women with continued poor health and those with worsened health had significantly increased risk of CVD incidence, CVD-specific death and all-cause death relative to women with continued good health. Both major and minor declines in physical health were associated with an increased risk of these outcomes relative to women with no change in physical health. Only major declines in mental health were associated with poor prognosis., Conclusions: changes in physical and mental health over 3 years were independently associated with subsequent CVD events., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Epidemiological studies suggest that a single moderate-to-severe traumatic brain injury (TBI) is associated with an increased risk of neurodegenerative disease, including Alzheimer's disease (AD) and Parkinson's disease (PD). Histopathological studies describe complex neurodegenerative pathologies in individuals exposed to single moderate-to-severe TBI or repetitive mild TBI, including chronic traumatic encephalopathy (CTE). However, the clinicopathological links between TBI and post-traumatic neurodegenerative diseases such as AD, PD, and CTE remain poorly understood. Here, we describe the methodology of the Late Effects of TBI (LETBI) study, whose goals are to characterize chronic post-traumatic neuropathology and to identify in vivo biomarkers of post-traumatic neurodegeneration. LETBI participants undergo extensive clinical evaluation using National Institutes of Health TBI Common Data Elements, proteomic and genomic analysis, structural and functional magnetic resonance imaging (MRI), and prospective consent for brain donation. Selected brain specimens undergo ultra-high resolution ex vivo MRI and histopathological evaluation including whole-mount analysis. Co-registration of ex vivo and in vivo MRI data enables identification of ex vivo lesions that were present during life. In vivo signatures of postmortem pathology are then correlated with cognitive and behavioral data to characterize the clinical phenotype(s) associated with pathological brain lesions. We illustrate the study methods and demonstrate proof of concept for this approach by reporting results from the first LETBI participant, who despite the presence of multiple in vivo and ex vivo pathoanatomic lesions had normal cognition and was functionally independent until her mid-80s. The LETBI project represents a multidisciplinary effort to characterize post-traumatic neuropathology and identify in vivo signatures of postmortem pathology in a prospective study.

Diffusion weighted MRI has become ubiquitous in many areas of medicine, including cancer diagnosis and treatment response monitoring. Reproducibility of diffusion metrics is essential for their acceptance as quantitative biomarkers in these areas. We examined the variability in the apparent diffusion coefficient (ADC) obtained from both postprocessing software implementations utilized by the NCI Quantitative Imaging Network and online scan time-generated ADC maps. Phantom and in vivo breast studies were evaluated for two ([Formula: see text]) and four ([Formula: see text]) [Formula: see text]-value diffusion metrics. Concordance of the majority of implementations was excellent for both phantom ADC measures and in vivo [Formula: see text], with relative biases [Formula: see text] ([Formula: see text]) and [Formula: see text] (phantom [Formula: see text]) but with higher deviations in ADC at the lowest phantom ADC values. In vivo [Formula: see text] concordance was good, with typical biases of [Formula: see text] to 3% but higher for online maps. Multiple b -value ADC implementations were separated into two groups determined by the fitting algorithm. Intergroup mean ADC differences ranged from negligible for phantom data to 2.8% for [Formula: see text] in vivo data. Some higher deviations were found for individual implementations and online parametric maps. Despite generally good concordance, implementation biases in ADC measures are sometimes significant and may be large enough to be of concern in multisite studies.

Background: The role of occupational prestige, a direct measure of the perceived status of job and job holder, in inflammation is unknown. To contribute to understanding the pathways by which socioeconomic position (SEP) is associated with inflammation, we aimed to estimate the direct effects of education, income and occupational prestige on C-reactive protein (CRP) and to describe the relationship between these markers and CRP., Methods: The study was based on 2026 post-menopausal women enrolled in the Women's Health Initiative-Observational Study. Occupational prestige was determined by linking a text description of longest held occupation with a social status item from the Occupational Information Network. Path analysis was employed to estimate direct and mediated effects., Results: The study suggests that higher levels of education, income, and occupational prestige are associated with 8% (95% CI as percentage change -12, -4), 5% [95% CI (-8, -2) and 4% (95% CI - 7, -1)] lower levels of CRP, respectively. The inverse association between education and CRP was explained by the effect of education on income and occupational prestige. The effect of occupational prestige on CRP was independent of mediators in the model., Conclusions: The findings indicate that education may work to influence CRP primarily through increasing income and occupational prestige and provides evidence that occupational prestige captures a unique aspect of SEP., (© The Author 2017. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.)

Background: Experimental evidence correlates anesthetic exposure during early development with neuronal and glial injury and death, as well as behavioral and cognitive impairments, in young animals. Several, although not all, retrospective human studies of neurocognitive and behavioral disorders after childhood exposure to anesthesia suggest a similar association. Few studies have specifically investigated the effects of infant anesthesia exposure on subsequent neurobehavioral development. Using a highly translational nonhuman primate model, the authors investigated the potential dose-dependent effects of anesthesia across the first year of development., Methods: The authors examined the effects of single or multiple early postnatal isoflurane exposures on subsequent behavioral development in 24 socially reared rhesus macaques. Infants were exposed to 5 h of isoflurane anesthesia once, three times (ISO-3), or not at all (control). The authors assessed reflex development and anxiety using standardized tests. At approximately 1 yr, infants (n = 23) were weaned and housed indoors with 5 to 6 other subjects. The authors recorded their response to this move and reassessed anxiety., Results: Compared to controls, animals exposed to repeated isoflurane (ISO-3) presented with motor reflex deficits at 1 month (median [range]: ISO-3 = 2 [1 to 5] vs. control = 5 [3 to 7]; P < 0.005) and responded to their new social environment with increased anxiety (median [range]: ISO-3 = 0.4 bouts/min [0.2 to 0.6]; control = 0.25 bouts/min [0.1 to 0.3]; P = 0.05) and affiliative/appeasement behavior (median [range]: ISO-3 = 0.1 [0 to 0.2]; control = 0 bouts/min [0 to 0.1]; P < 0.01) at 12 months. There were no statistically significant behavioral alterations after single isoflurane exposure., Conclusions: Neonatal exposure to isoflurane, particularly when repeated, has long-term behavioral consequences affecting both motor and socioemotional aspects of behavior., Competing Interests: None of the authors have any conflict of interest.

Purpose: To characterize spatial patterns of T2* in the placenta of the rhesus macaque (Macaca mulatta), to correlate these patterns with placental perfusion determined using dynamic contrast-enhanced MRI (DCE-MRI), and to evaluate the potential for using the blood oxygen level-dependent effect to quantify placental perfusion without the use of exogenous contrast reagent., Methods: MRI was performed on three pregnant rhesus macaques at gestational day 110. Multiecho spoiled gradient echo measurements were used to compute maps of T2*. Spatial maxima in these maps were compared with foci of early enhancement determined by DCE-MRI., Results: Local maxima in T2* maps were strongly correlated with spiral arteries identified by DCE-MRI, with mean spatial separations ranging from 2.34 to 6.11 mm in the three animals studied. Spatial patterns of R2* ( = 1/ T2*) within individual placental lobules can be quantitatively analyzed using a simple model to estimate fetal arterial oxyhemoglobin concentration [Hbo,f] and a parameter viPS/Φ, reflecting oxygen transport to the fetus. Estimated mean values of [Hbo,f] ranged from 4.25 mM to 4.46 mM, whereas viPS/Φ ranged from 2.80 × 10 5 cm -3 to 1.61 × 10 6 cm -3 ., Conclusions: Maternal spiral arteries show strong spatial correlation with foci of extended T2* observed in the primate placenta. A simple model of oxygen transport accurately describes the spatial dependence of R2* within placental lobules and enables assessment of placental function and oxygenation without requiring administration of an exogenous contrast reagent. Magn Reson Med 76:1551-1562, 2016. © 2015 International Society for Magnetic Resonance in Medicine., (© 2015 International Society for Magnetic Resonance in Medicine.)

Background: Strategies for identifying the most relevant psychosocial predictors in studies of racial/ethnic minority women's health are limited because they largely exclude cultural influences and they assume that psychosocial predictors are independent. This paper proposes and tests an empirical solution., Methods: Hierarchical cluster analysis, conducted with data from 140,652 Women's Health Initiative participants, identified clusters among individual psychosocial predictors. Multivariable analyses tested associations between clusters and health outcomes., Results: A Social Cluster and a Stress Cluster were identified. The Social Cluster was positively associated with well-being and inversely associated with chronic disease index, and the Stress Cluster was inversely associated with well-being and positively associated with chronic disease index. As hypothesized, the magnitude of association between clusters and outcomes differed by race/ethnicity., Conclusions: By identifying psychosocial clusters and their associations with health, we have taken an important step toward understanding how individual psychosocial predictors interrelate and how empirically formed Stress and Social clusters relate to health outcomes. This study has also demonstrated important insight about differences in associations between these psychosocial clusters and health among racial/ethnic minorities. These differences could signal the best pathways for intervention modification and tailoring.

This paper presents an approach to 3-D diffusion tensor image (DTI) reconstruction from multi-slice diffusion weighted (DW) magnetic resonance imaging acquisitions of the moving fetal brain. Motion scatters the slice measurements in the spatial and spherical diffusion domain with respect to the underlying anatomy. Previous image registration techniques have been described to estimate the between slice fetal head motion, allowing the reconstruction of 3D a diffusion estimate on a regular grid using interpolation. We propose Approach to Unified Diffusion Sensitive Slice Alignment and Reconstruction (AUDiSSAR) that explicitly formulates a process for diffusion direction sensitive DW-slice-to-DTI-volume alignment. This also incorporates image resolution modeling to iteratively deconvolve the effects of the imaging point spread function using the multiple views provided by thick slices acquired in different anatomical planes. The algorithm is implemented using a multi-resolution iterative scheme and multiple real and synthetic data are used to evaluate the performance of the technique. An accuracy experiment using synthetically created motion data of an adult head and an experiment using synthetic motion added to sedated fetal monkey dataset show a significant improvement in motion-trajectory estimation compared to current state-of-the-art approaches. The performance of the method is then evaluated on challenging but clinically typical in utero fetal scans of four different human cases, showing improved rendition of cortical anatomy and extraction of white matter tracts. While the experimental work focuses on DTI reconstruction (second-order tensor model), the proposed reconstruction framework can employ any 5-D diffusion volume model that can be represented by the spatial parameterizations of an orientation distribution function.

Folding of the cerebral cortical surface is a critical process in human brain development, yet despite decades of indirect study and speculation the mechanics of the process remain incompletely understood. Leading hypotheses have focused on the roles of circumferential expansion of the cortex, radial growth, and internal tension in neuronal fibers (axons). In this article, we review advances in the mathematical modeling of growth and morphogenesis and new experimental data, which together promise to clarify the mechanical basis of cortical folding. Recent experimental studies have illuminated not only the fundamental cellular and molecular processes underlying cortical development, but also the stress state and mechanical behavior of the developing brain. The combination of mathematical modeling and biomechanical data provides a means to evaluate hypothesized mechanisms objectively and quantitatively, and to ensure that they are consistent with physical law, given plausible assumptions and reasonable parameter values., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Physical and Mental Component Summary (PCS, MCS, respectively) scales of SF- 36 health-related-quality-of-life have been associated with all-cause and cardiovascular disease (CVD) mortality. Their relationships with CVD incidence are unclear. This study purpose was to test whether PCS and/or MCS were associated with CVD incidence and death., Methods: Postmenopausal women (aged 50-79 years) in control groups of the Women's Health Initiative clinical trials (n = 20,308) completed the SF-36 and standardized questionnaires at trial entry. Health outcomes, assessed semi-annually, were verified with medical records. Cox regressions assessed time to selected outcomes during the trial phase (1993-2005)., Results: A total of 1075 incident CVD events, 204 CVD-specific deaths, and 1043 total deaths occurred during the trial phase. Women with low versus high baseline PCS scores had less favorable health profiles at baseline. In multivariable models adjusting for baseline confounders, participants in the lowest PCS quintile (reference = highest quintile) exhibited 1.8 (95%CI: 1.4, 2.3), 4.7 (95%CI: 2.3, 9.4), and 2.1 (95%CI: 1.7, 2.7) times greater risk of CVD incidence, CVD-specific death, and total mortality, respectively, by trial end; whereas, MCS was not significantly associated with CVD incidence or death., Conclusion: Physical health, assessed by self-report of physical functioning, is a strong predictor of CVD incidence and death in postmenopausal women; similar self-assessment of mental health is not. PCS should be evaluated as a screening tool to identify older women at high risk for CVD development and death.

Background: Little is known about the development of posttraumatic stress disorder (PTSD) over time among women diagnosed with breast cancer. This study examines changes in PTSD symptoms in the first 6 months after diagnosis and assesses racial/ethnic differences in PTSD symptomatology over time., Methods: We recruited women with newly diagnosed breast cancer, stages I to III, from three sites in the United States. Three telephone interviews were conducted: baseline at about 2 to 3 months after diagnosis, first follow-up at 4 months after diagnosis, and second follow-up at 6 months after diagnosis. We measured traumatic stress in each interview using the Impact of Events Scale; recorded sociodemographic, tumor, and treatment factors; and used generalized estimating equations and polytomous logistic regression modeling to examine the associations between variables of interest and PTSD., Results: Of 1139 participants, 23% reported symptoms consistent with a diagnosis of PTSD at baseline, 16.5% at first follow-up, and 12.6% at the second follow-up. Persistent PTSD was observed among 12.1% participants, as defined by having PTSD at two consecutive interviews. Among participants without PTSD at baseline, 6.6% developed PTSD at the first follow-up interview. Younger age at diagnosis, being black (odds ratio [OR] = 1.48 vs white, 95% confidence interval [CI] =1.04 to 2.10), and being Asian (OR = 1.69 vs white, 95% CI = 1.10 to 2.59) were associated with PTSD., Conclusions: Nearly one-quarter of women newly diagnosed with breast cancer reported symptoms consistent with PTSD shortly after diagnosis, with increased risk among black and Asian women. Early identification of PTSD may present an opportunity to provide interventions to manage symptoms.

Apolipoprotein-ε4 (APOE-ε4) is a major genetic risk factor for cognitive decline, Alzheimer's disease (AD) and early mortality. An accelerated rate of biological aging could contribute to this increased risk. Here, we determined whether APOE-ε4 status impacts leukocyte telomere length (TL) and the rate of cellular senescence in healthy mid-life women and, further, whether hormone replacement therapy (HT) modifies this association. Post-menopausal women (N = 63, Mean age = 57.7), all HT users for at least one year, were enrolled in a randomized longitudinal study. Half of the participants (N = 32) remained on their HT regimen and half (N = 31) went off HT for approximately two years (Mean  = 1.93 years). Participants included 24 APOE-ε4 carriers and 39 non-carrier controls. Leukocyte TL was measured at baseline and the end of year 2 using quantitative polymerase chain reaction. Logistic regression analysis indicated that the odds of an APOE-ε4 carrier exhibiting telomere shortening (versus maintenance/growth) over the 2-year study were more than 6 (OR  = 6.26, 95% CI  = 1.02, 38.49) times higher than a non-carrier, adjusting for established risk factors and potential confounds. Despite the high-functioning, healthy mid-life status of study participants, APOE-ε4 carriers had marked telomere attrition during the 2-year study window, the equivalent of approximately one decade of additional aging compared to non-carriers. Further analyses revealed a modulatory effect of hormone therapy on the association between APOE status and telomere attrition. APOE-ε4 carriers who went off their HT regimen exhibited TL shortening, as predicted for the at-risk population. APOE-ε4 carriers who remained on HT, however, did not exhibit comparable signs of cell aging. The opposite pattern was found in non-carriers. The results suggest that hormone use might buffer against accelerated cell aging in mid-life women at risk for dementia. Importantly, for non-carrier women there was no evidence that HT conferred protective effects on telomere dynamics.

A crucial step in studying brain connectivity is the definition of the Regions Of Interest (ROI's) which are considered as nodes of a network graph. These ROI's identified in structural imaging reflect consistent functional regions in the anatomies being compared. However in serial studies of the developing fetal brain such functional and associated structural markers are not consistently present over time. In this study we adapt two non-atlas based parcellation schemes to study the development of connectivity networks of a fetal monkey brain using Diffusion Weighted Imaging techniques. Results demonstrate that the fetal brain network exhibits small-world characteristics and a pattern of increased cluster coefficients and decreased global efficiency. These findings may provide a route to creating a new biomarker for healthy fetal brain development.

Background: Little is known about the long-term impact of comorbidity among women with breast cancer., Methods: We studied a prospective cohort of 2,272 women with breast cancer, who were recruited following initial breast cancer treatment. Associations of the Charlson comorbidity index (CCI) and hypertension with survival were evaluated in delayed entry Cox proportional hazards models., Results: During a median follow-up of nine years, higher CCI scores were independently associated with an increased risk of death from all causes [HR, 1.32; 95% confidence interval (CI), 1.13-1.54] and from nonbreast cancer causes (HR, 1.55; 95% CI, 1.19-2.02), but not from breast cancer (HR, 1.14; 95% CI, 0.93-1.41). Hypertension was independently associated with an increased risk of death from all causes (HR, 1.55; 95% CI, 1.20-1.99), from nonbreast cancer causes (HR, 1.67; 95% CI, 1.10-2.54), and from breast cancer (HR, 1.47; 95% CI, 1.03-2.09), but these associations were no longer significant after adjustment for antihypertensive medication. The relationship between the CCI and overall survival was the strongest among women with stage I disease (stage I, HR, 1.65; 95% CI, 1.26-2.16 vs. stage III, HR, 0.53; 95% CI, 0.23-1.25)., Conclusion: The CCI was independently associated with lower overall and nonbreast cancer survival, but not with breast cancer-specific survival., Impact: Comorbidity may play an important role in breast cancer outcomes., (©2012 AACR)

Of the acetylcholine muscarinic receptors, the type 1 (M1) and type 2 (M2) receptors are expressed at the highest levels in the prefrontal cortex (PFC) and hippocampus, brain regions important for cognition. As equivocal findings of age-related changes of M1 and M2 in the nonhuman primate brain have been reported, we first assessed age-related changes in M1 and M2 in the PFC and hippocampus using saturation binding assays. Maximum M1 receptor binding, but not affinity of M1 receptor binding, decreased with age. In contrast, the affinity of M2 receptor binding, but not maximum M2 receptor binding, increased with age. To determine if in the elderly cognitive performance is associated with M1 or M2 function, we assessed muscarinic function in elderly female rhesus macaques in vivo using a scopolamine challenge pharmacological magnetic resonance imaging and in vitro using saturation binding assays. Based on their performance in a spatial maze, the animals were classified as good spatial performers (GSP) or poor spatial performers (PSP). In the hippocampus, but not PFC, the GSP group showed a greater change in T(2)*-weighted signal intensity after scopolamine challenge than the PSP group. The maximum M1 receptor binding and receptor binding affinity was greater in the GSP than the PSP group, but no group difference was found in M2 receptor binding. Parameters of circadian activity positively correlated with the difference in T(2)*-weighted signal intensity before and after the challenge, the maximum M1 receptor binding, and the M1 receptor binding affinity. Thus, while in rhesus macaques, there are age-related decreases in M1 and M2 receptor binding, in aged females, hippocampal M1, but not M2, receptor function is associated with spatial learning and memory and circadian activity.