Association between Body Iron Status and Cognitive Task Performance in a Nationally Representative Sample of Older Adults.

Iron is an essential micronutrient that is necessary for proper cognitive function. However, the dose-response relationship between body iron status and cognitive function remains unclear. The objective of this study was to investigate the association between serum ferritin concentrations, an indicator of body iron status, and cognitive function in older adults. Based on the National Health and Nutrition Examination Survey (NHANES) 1999 -2002 in the United States, nationally representative data was collected from 2,567 adults aged 60 years and older who had objectively measured serum ferritin levels and cognitive performance. High ferritin levels were defined as a serum ferritin level >200 ng/mL in women and >300 ng/mL in men. Low ferritin levels were defined as a serum ferritin level <30 ng/mL. The digit symbol substitution test (DSST) was employed to assess cognitive function. Multivariable logistic regression analyses with survey weights were performed after the DSST was dichotomized at the median score. The weighted prevalence of adults with normal, low, and high serum ferritin levels were 73.98%, 9.12%, and 16.91%, respectively. A U-shaped association between serum ferritin concentrations and cognitive task performance was observed. After adjusting for demographic, socioeconomic, lifestyle, and C-reactive protein factors, the odds ratio (95% confidence intervals) for lower cognitive performance was 1.39 (1.11, 1.74) in adults with high ferritin levels and 1.38 (0.86, 2.22) in adults with low ferritin levels, compared with those with normal ferritin levels. The association between serum ferritin levels and lower cognitive performance was stronger in adults aged 60 to 69 years old than those aged 70 years and older. In conclusion, in a nationally representative sample of older adults in the United States, a high serum ferritin level was significantly associated with worse cognitive task performance. Thus, the relationship between low serum ferritin concentrations and cognitive task performance warrants further investigation.

Risk of Adverse Cardiovascular Outcomes in Postmenopausal Women with Inflammatory Bowel Disease.

BACKGROUND: Individuals with inflammatory bowel disease (IBD) who lack traditional cardiovascular disease (CVD) risk factors, such as young females, are observed to experience adverse CVD outcomes. Whether women with IBD have increased CVD risk after the menopause transition is unclear. METHODS: We conducted a survival analysis of Women's Health Initiative (WHI) participants and excluded those with missing IBD diagnosis, model covariate data, follow-up data, or a baseline history of the following CVD outcomes: coronary heart disease (CHD), ischemic stroke, venous thromboembolism (VTE), peripheral arterial disease (PAD). Risk of outcomes between IBD and non-IBD women was performed using Cox proportional hazard models, stratified by WHI trial and follow-up. Models were adjusted for age, socio-demographics, comorbidities (e.g., hypertension, diabetes, hypercholesterolemia, etc.), family history, and lifestyle factors (e.g., smoking, alcohol, physical activity, body mass index, etc.). RESULTS: Of 134,022 WHI participants meeting inclusion criteria, 1367 (1.0%) reported IBD at baseline. Mean baseline age was 63.4 years. After adjusting for age and other confounders, no significant difference was observed between IBD and non-IBD women for the risk of CHD (HR 0.96, 95% CI 0.73-1.24), VTE (HR 1.11, 95% CI 0.81-1.52) or PAD (HR 0.64, 95% CI 0.28-1.42). After adjusting for age, risk of ischemic stroke was significantly higher (HR 1.41, 95% CI 1.06-1.88) in IBD than non-IBD women. With further adjustment, the excess risk of ischemic stroke among IBD women was attenuated and no longer statistically significant (HR 1.31, 95% CI 0.98-1.76). CONCLUSIONS: Among postmenopausal women with IBD, risk of ischemic stroke may be higher than in non-IBD women.

Small Felids Coexist in Mixed-Use Landscape in the Bolivian Amazon.

In the face of global species loss, it is paramount to understand the effects of human activity on vulnerable species, particularly in highly diverse, complex systems. The Greater Madidi Landscape in the Bolivian Amazon includes several biodiverse protected areas that were created with the goal of sustaining healthy and diverse ecosystems while not impeding the livelihoods of local indigenous peoples. In this study, we sought to use camera trap data and single-species occupancy analysis to assess the impacts of different forms of human activity on four species of small felids: ocelots (Leopardus pardalis), margays (Leopardus wiedii), jaguarundi (Herpailurus yagouaroundi), and oncilla (Leopardus tigrinus). We modeled both human variables (proximity to indigenous communities, roads, and tourist camps) and non-human variables (terrain ruggedness, proximity to rivers, canopy height, prey availability, and large cat abundance). Margay occupancy was unaffected by any of these human variables and ocelots showed only weak evidence of being affected by tourism. Ocelots were particularly pervasive throughout the study area and were consistently estimated to have high occupancy probability. We did not obtain sufficient data on jaguarundi or oncilla to reliably model these effects. Our results indicate that small cats successfully coexist both with each other and with the surrounding human activity in this unique landscape, which serves as a model for global protected area management.

Biomarker-assessed total energy intake and its cohort study association with all-cause mortality in postmenopausal females.

BACKGROUND: The association of total energy intake (EI) with all-cause mortality is uncertain as are the dependencies of this association on age and weight change history. OBJECTIVES: To identify an EI biomarker suitable for use in epidemiologic association studies and to study EI associations with total mortality in a Women's Health Initiative (WHI) cohort of postmenopausal United States females (1993-present). METHODS: EI biomarkers were developed based on doubly labeled water (DLW) total energy expenditure (TEE) and weight variation during the 2-wk DLW protocol period using the energy balance method in an embedded feeding study (n = 153). This along with 2 earlier WHI nutrition biomarker studies having TEE assessments (n = 1131 total), with 14.6 y (median) follow-up, constituted a prospective cohort for the study of EI and all-cause mortality. RESULTS: An empirical biomarker for log(EI) was developed that had a correlation of 0.73 with log(feeding study-consumed EI). The overall association between EI and mortality was nonsignificant. The association, however, depended on age (P = 0.009), with lower EI associated with lower mortality at younger ages, and also on preceding weight change history (P = 0.03). Among participants with stable or increasing weight, mortality hazard ratios (95% confidence intervals [CIs]) for a 12% lower EI were 0.66 (95% CI: 0.51, 0.87) at age 60, 0.84 (95% CI: 0.72, 0.98) at age 70, and 1.06 (95% CI: 0.87, 1.29) at age 80. Corresponding values for participants having preceding weight loss were 0.83 (95% CI: 0.61, 1.12) at age 60, 1.05 (95% CI: 0.87, 1.26) at age 70, and 1.33 (95% CI: 1.08, 1.63) at age 80. A previously considered EI biomarker, using a theoretical model for variation in body fat and fat-free mass components over time, gave similar results following rescaling. CONCLUSIONS: Lower EI is associated with lower all-cause mortality among younger postmenopausal females with stable or increasing weight and with higher mortality among older females with weight loss. This study was registered with clinicaltrials.gov as NCT00000611.

Bisphenol S, bisphenol F, bisphenol a exposure and body composition in US adults.

Bisphenol S (BPS) and bisphenol F (BPF) are increasingly used to replace bisphenol A (BPA), an endocrine-disrupting chemical with putative obesogenic properties; whether and how BPS and BPF affect adiposity in humans remains to be determined. Therefore, we examined the association of BPA, BPS， and BPF with body composition among US adults. We included 1787 participants aged 20-59 years old in the National Health and Nutrition Examination Survey 2013-2016 who had information on urinary BPA, BPS, and BPF concentrations, and body composition measured using dual-energy x-ray absorptiometry. After full adjustment for potential confounders in linear regression models, BPA was significantly associated with the % body fat of the whole body, arm, and leg, with the ß (95% CI) for the highest quartile vs. the lowest quartile of 1.34 (95%CI [0.11, 2.58], P = 0.03), 1.60 (95%CI [0.20, 3.00], P = 0.03), and 1.63 (95%CI [0.24, 3.02], P = 0.02), respectively. No association between BPA and lean mass was found. For BPS, significant associations were found for % body fat of the whole body (ß [95% CI] = 1.42 [0.49, 2.36], P = 0.004), trunk (ß[95% CI] = 1.92 [0.86, 2.97], P = 0.001), and arm (ß [95% CI] = 1.60 [0.49, 2.70], P = 0.01), as well as lean mass of the whole body (ß [95% CI] = 2610.6 [1324.3, 3896.8], P < 0.001), trunk (ß [95% CI] = 1467.0 [745.3, 2188.7], P < 0.001), arm (ß [95% CI] = 113.4 [10.3, 216.5], P = 0.03), and leg (ß [95% CI] = 431.5 [219.6, 643.4], P < 0.001), comparing the third quartile vs. the lowest quartile. No significant association was observed between BPF and % body fat and lean mass. Results suggest that higher BPA levels were significantly associated with greater % body fat of the whole body and limbs, and there was suggestive evidence that BPS levels were associated with both % body fat and lean mass of the whole body and body parts in a nonmonotonic relationship.

Association of type 2 diabetes mellitus with dementia-related and non-dementia-related mortality among postmenopausal women: A secondary competing risks analysis of the women's health initiative.

INTRODUCTION: Alzheimer's disease (AD) and AD-related dementias (ADRD) are leading causes of death among older adults in the United States. Efforts to understand risk factors for prevention are needed. METHODS: Participants (n = 146,166) enrolled in the Women's Health Initiative without AD at baseline were included. Diabetes status was ascertained from self-reported questionnaires and deaths attributed to AD/ADRD from hospital, autopsy, and death records. Competing risk regression models were used to estimate the cause-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for the prospective association of type 2 diabetes mellitus (T2DM) with AD/ADRD and non-AD/ADRD mortality. RESULTS: There were 29,393 treated T2DM cases and 8628 AD/ADRD deaths during 21.6 (14.0-23.5) median (IQR) years of follow-up. Fully adjusted HRs (95% CIs) of the association with T2DM were 2.94 (2.76-3.12) for AD/ADRD and 2.65 (2.60-2.71) for the competing risk of non-AD/ADRD mortality. DISCUSSION: T2DM is associated with AD/ADRD and non-AD/ADRD mortality. HIGHLIGHTS: Type 2 diabetes mellitus is more strongly associated with Alzheimer's disease (AD)/AD and related dementias (ADRD) mortality compared to the competing risk of non-AD/ADRD mortality among postmenopausal women. This relationship was consistent for AD and ADRD, respectively. This association is strongest among participants without obesity or hypertension and with younger age at baseline, higher diet quality, higher physical activity, higher alcohol consumption, and older age at the time of diagnosis of type 2 diabetes mellitus.

Stressful life events, social support, and epigenetic aging in the Women's Health Initiative.

BACKGROUND: Elevated psychosocial stress has been linked with accelerated biological aging, including composite DNA methylation (DNAm) markers that predict aging-related outcomes ("epigenetic age"). However, no study has examined whether stressful life events (SLEs) are associated with epigenetic age acceleration in postmenopausal women, an aging population characterized by increased stress burden and disease risk. METHODS: We leveraged the Women's Health Initiative, a large muti-ancestry cohort of postmenopausal women with available psychosocial stress measures over the past year and epigenomic data. SLEs and social support were ascertained via self-report questionnaires. Whole blood DNAm array (450 K) data were used to calculate five DNAm-based predictors of chronological age, health span and life span, and telomere length (HorvathAge, HannumAge, PhenoAge, GrimAge, DNAmTL). RESULTS: After controlling for potential confounders, higher SLE burden was significantly associated with accelerated epigenetic aging, as measured by GrimAge (ß: 0.34, 95% CI: 0.08, 0.59) and DNAmTL (ß: -0.016, 95% CI: -0.028, -0.004). Exploratory analyses showed that SLEs-GrimAge associations were stronger in Black women as compared to other races/ethnicities and in those with lower social support levels. In women with lower social support, SLEs-DNAmTL associations showed opposite association in Hispanic women as compared to other race/ethnicity groups. CONCLUSIONS: Our findings suggest that elevated stress burden is associated with accelerated epigenetic aging in postmenopausal women. Lower social support and/or self-reported race/ethnicity may modify the association of stress with epigenetic age acceleration. These findings advance understanding of how stress may contribute to aging-related outcomes and have important implications for disease prevention and treatment in aging women.

Association of macular pigment optical density with retinal layer thicknesses in eyes with and without manifest primary open-angle glaucoma.

OBJECTIVE: To investigate associations between baseline macular pigment optical density (MPOD) and retinal layer thicknesses in eyes with and without manifest primary open-angle glaucoma (POAG) in the Carotenoids in Age-Related Eye Disease Study 2 (CAREDS2). METHODS AND ANALYSIS: MPOD was measured at CAREDS baseline (2001-2004) via heterochromatic flicker photometry (0.5° from foveal centre). Peripapillary retinal nerve fibre layer (RNFL), macular ganglion cell complex (GCC), ganglion cell layer (GCL), inner plexiform layer (IPL), and RNFL thicknesses were measured at CAREDS2 (2016-2019) via spectral-domain optical coherence tomography. Associations between MPOD and retinal thickness were assessed using multivariable linear regression. RESULTS: Among 742 eyes (379 participants), manifest POAG was identified in 50 eyes (32 participants). In eyes without manifest POAG, MPOD was positively associated with macular GCC, GCL and IPL thicknesses in the central subfield (P-trend ≤0.01), but not the inner or outer subfields. Among eyes with manifest POAG, MPOD was positively associated with macular GCC, GCL, IPL and RNFL in the central subfield (P-trend ≤0.03), but not the inner or outer subfields, and was positively associated with peripapillary RNFL thickness in the superior and temporal quadrants (P-trend≤0.006). CONCLUSION: We observed a positive association between MPOD and central subfield GCC thickness 15 years later. MPOD was positively associated with peripapillary RNFL superior and temporal quadrant thicknesses among eyes with manifest POAG. Our results linking low MPOD to retinal layers that are structural indicators of early glaucoma provide further evidence that carotenoids may be protective against manifest POAG.

Bilateral Oophorectomy and Colorectal Cancer Incidence and Mortality in the Women's Health Initiative.

BACKGROUND: The few cohort studies examining oophorectomy and colorectal cancer risk provide mixed results. Therefore, we examined this issue in Women's Health Initiative Observational Study participants. METHODS: A total of 71,312 postmenopausal women were followed for 22.1 years (median). At enrollment, 55,643 (78%) had intact ovaries and 15,669 (22%) had undergone a bilateral oophorectomy. Colorectal cancers were verified by central medical record review with mortality findings enhanced by National Death Index queries. RESULTS: With 1,421 incident colorectal cancers, 450 colorectal cancer-specific mortalities, after controlling for covariates, bilateral oophorectomy was not associated with colorectal cancer incidence or colorectal cancer mortality. CONCLUSIONS: No significant associations between oophorectomy and colorectal cancer incidence and mortality were seen in a large cohort study with long follow-up. IMPACT: As the oophorectomy and colorectal cancer question remains open, further studies of high quality, even with null findings, should be encouraged.

Association Between the Healthy Lifestyle Index and Risk of Multimorbidity in the Women's Health Initiative.

BACKGROUND: Multimorbidity, defined as the presence of 2 or more chronic health conditions, is increasingly common among older adults. The combination of lifestyle characteristics such as diet quality, smoking status, alcohol intake, physical activity (PA), sleep duration, and body fat as assessed by body mass index (BMI) or waist circumference, and risk of multimorbidity are not well understood. OBJECTIVES: We investigated the association between the healthy lifestyle index (HLI), generated by combining indicators of diet quality, smoking, alcohol, PA, sleep amount, and BMI, and risk of multimorbidity, a composite outcome that included cardiovascular disease (CVD), diabetes, cancer, and fracture. METHODS: We studied 62 037 postmenopausal women aged 50-79 years at enrollment in the Women's Health Initiative, with no reported history of CVD, diabetes, cancer, or fracture at baseline. Lifestyle characteristics measured at baseline were categorized and a score (0-4) was assigned to each category. The combined HLI (0-24) was grouped into quintiles, with higher quintiles indicating a healthier lifestyle. Multivariable adjusted estimates of hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the risk of developing multimorbidity were obtained using Cox proportional hazard models. RESULTS: Over an average follow-up period of 16.3 years, 5 656 women developed multimorbidity. There was an inverse association between the HLI levels and risk of multimorbidity (compared to the HLI_1st quintile: HR_2nd quintile = 0.81 95% CI 0.74-0.83, HR_3rd quintile = 0.77 95% CI 0.71-0.83, HR_4th quintile = 0.70 95% CI 0.64-0.76, and HR_5th quintile = 0.60 95% CI 0.54-0.66; p trend < .001). Similar associations were observed after stratification by age or BMI categories. CONCLUSIONS: Among postmenopausal women, higher levels of the HLI were associated with a reduced risk of developing multimorbidity.

Metabolomics Biomarkers for Fatty Acid Intake and Biomarker-Calibrated Fatty Acid Associations with Chronic Disease Risk in Postmenopausal Women.

BACKGROUND: A substantial observational literature relating specific fatty acid classes to chronic disease risk may be limited by its reliance on self-reported dietary data. OBJECTIVES: We aimed to develop biomarkers for saturated (SFA), monounsaturated (MUFA), and polyunsaturated (PUFA) fatty acid densities, and to study their associations with cardiovascular disease (CVD), cancer, and type 2 diabetes (T2D) in Women's Health Initiative (WHI) cohorts. METHODS: Biomarker equations were based primarily on serum and urine metabolomics profiles from an embedded WHI human feeding study (n = 153). Calibration equations were based on biomarker values in a WHI nutritional biomarker study (n = 436). Calibrated intakes were assessed in relation to disease incidence in larger WHI cohorts (n = 81,894). Participants were postmenopausal women, aged 50-79 when enrolled at 40 United States Clinical Centers (1993-1998), with a follow-up period of ∼20 y. RESULTS: Biomarker equations meeting criteria were developed for SFA, MUFA, and PUFA densities. That for SFA density depended somewhat weakly on metabolite profiles. On the basis of our metabolomics platforms, biomarkers were insensitive to trans fatty acid intake. Calibration equations meeting criteria were developed for SFA and PUFA density, but not for MUFA density. With or without biomarker calibration, SFA density was associated positively with risk of CVD, cancer, and T2D, but with small hazard ratios, and CVD associations were not statistically significant after controlling for other dietary variables, including trans fatty acid and fiber intake. Following this same control, PUFA density was not significantly associated with CVD risk, but there were positive associations for some cancers and T2D, with or without biomarker calibration. CONCLUSIONS: Higher SFA and PUFA diets were associated with null or somewhat higher risk for clinical outcomes considered in this population of postmenopausal United States women. Further research is needed to develop even stronger biomarkers for these fatty acid densities and their major components. This study is registered with clinicaltrials.gov identifier: NCT00000611.

Impact of COVID-19 pandemic on nonpharmacological pain management trials in military and veteran healthcare settings: an evaluation informed by implementation science.

The coronavirus disease (COVID-19) pandemic disrupted healthcare and clinical research, including a suite of 11 pragmatic clinical trials (PCTs), across clinics within the Department of Veterans Affairs (VA) and the Department of Defense (DOD). These PCTs were designed to evaluate an array of nonpharmacological treatments and models of care for treatment of patients with pain and co-occurring conditions. The aims of the study are to (a) describe modifications to PCTs and interventions to address the evolving pandemic and (b) describe the application of implementation science methods for evaluation of those PCT modifications. The project used a two-phase, sequential, mixed-methods design. In Phase I, we captured PCT disruptions and modifications via a Research Electronic Data Capture questionnaire, using Periodic Reflections methods as a guide. In Phase II, we utilized the Framework for Reporting Adaptations and Modifications-Expanded (FRAME) taxonomy to develop a focus group interview guide and checklist that would provide more in-depth data than Phase I. Data were analyzed using directed content analysis. Phase I revealed that all PCTs made between two and six trial modifications. Phase II, FRAME-guided analyses showed that the key goals for modifying interventions were increasing treatment feasibility and decreasing patient exposure to COVID-19, while preserving intervention core elements. Context (format) modifications led eight PCTs to modify parts of the interventions for virtual delivery. Content modifications added elements to enhance patient safety; tailored interventions for virtual delivery (counseling, exercise, mindfulness); and modified interventions involving manual therapies. Implementation science methods identified near-real-time disruptions and modifications to PCTs focused on pain management in veteran and military healthcare settings.

Active-duty personnel and veterans often report pain and seek treatment in military and veteran healthcare settings. Nondrug treatments, such as self-care, counseling, exercise, and manual therapy, are recommended for most patients with chronic pain. The COVID-19 pandemic has affected clinical trials of these nondrug treatments in military and veteran populations. In this study, we explored how 11 research teams adapted study trials on pain to address COVID-19. Team members completed online questions, brief checklists, and a one-time focus group about how they modified their trials. Each of the 11 trials made 2 to 6 changes to their studies. Most paused or delayed recruitment efforts. Many shifted parts of the study to a virtual format. Goals for adapting treatments included improved feasibility and decreased patient exposure to COVID-19. Context or format changes increased virtual delivery of study treatments. Content changes focused on patient safety, tailoring treatments for virtual delivery, and offering varied manual therapies. Provider concerns about technology and patient willingness to seek in-person care during the pandemic also were factors driving changes. These findings may support the increased use of virtual care for pain management in military and veteran health settings.

Assessment of immune cell profiles among post-menopausal women in the Women's Health Initiative using DNA methylation-based methods.

BACKGROUND: Over the past decade, DNA methylation (DNAm)-based deconvolution methods that leverage cell-specific DNAm markers of immune cell types have been developed to provide accurate estimates of the proportions of leukocytes in peripheral blood. Immune cell phenotyping using DNAm markers, termed immunomethylomics or methylation cytometry, offers a solution for determining the body's immune cell landscape that does not require fresh blood and is scalable to large sample sizes. Despite significant advances in DNAm-based deconvolution, references at the population level are needed for clinical and research interpretation of these additional immune layers. Here we aim to provide some references for immune populations in a group of multi-ethnic post-menopausal American women. RESULTS: We applied DNAm-based deconvolution to a large sample of post-menopausal women enrolled in the Women's Health Initiative (baseline, N = 58) or the ancillary Long Life Study (WHI-LLS, N = 1237) to determine the reference ranges of 58 immune parameters, including proportions and absolute counts for 19 leukocyte subsets and 20 derived cell ratios. Participants were 50-94 years old at the time of blood draw, and N = 898 (69.3%) self-identified as White. Using linear regression models, we observed significant associations between age at blood draw and absolute counts and proportions of naïve B, memory CD4+, naïve CD4+, naïve CD8+, memory CD8+ memory, neutrophils, and natural killer cells. We also assessed the same immune profiles in a subset of paired longitudinal samples collected 14-18 years apart across N = 52 participants. Our results demonstrate high inter-individual variability in rates of change of leukocyte subsets over this time. And, when conducting paired t tests to test the difference in counts and proportions between the baseline visit and LLS visit, there were significant changes in naïve B, memory CD4+, naïve CD4+, naïve CD8+, memory CD8+ cells and neutrophils, similar to the results seen when analyzing the association with age in the entire cohort. CONCLUSIONS: Here, we show that derived cell counts largely reflect the immune profile associated with proportions and that these novel methods replicate the known immune profiles associated with age. Further, we demonstrate the value this methylation cytometry approach can add as a potential application in epidemiological studies.

Total energy expenditure as assessed by doubly labeled water and all-cause mortality in a cohort of postmenopausal women.

BACKGROUND: The association of TEE with all-cause mortality is uncertain, as is the dependence of this association on age. OBJECTIVES: To examine the association between TEE and all-cause mortality, and its age interaction, in a Women's Health Initiative (WHI) cohort of postmenopausal United States women (1992-present). METHODS: A cohort of 1131 WHI participants having DLW TEE assessment of ∼10.0 y (median) following WHI enrollment with ∼13.7 y (median) of subsequent follow-up, was used to study the EE associations with all-cause mortality. To enhance the comparability of TEE and total EI, key analyses excluded participants having >5% weight change between WHI enrollment and DLW assessment. The influence of participant age on mortality associations was examined, as was the ability of concurrent and earlier weight and height measurements to explain the results. RESULTS: There were 308 deaths following the TEE assessment through 2021. TEE was unrelated to overall mortality (P = 0.83) in this cohort of generally healthy, older (mean 71 y at TEE assessment) United States women. However, this potential association varied with age (P = 0.003). Higher TEE was associated with a higher mortality rate at the age of 60 y and a lower mortality rate at the age of 80 y. Within the weight-stable subset (532 participants, 129 deaths), TEE was weakly positively related to overall mortality (P = 0.08). This association also varied with age (P = 0.03), with mortality HRs (95% CIs) for a 20% increment in TEE of 2.33 (1.24, 4.36) at the age of 60 y, 1.49 (1.10, 2.02) at 70 y of age, and 0.96 (0.66, 1.38) at 80 y of age. This pattern remained, although was somewhat attenuated, following control for baseline weight and weight changes between WHI enrollment and TEE assessment. CONCLUSIONS: Higher EE is associated with higher all-cause mortality among younger postmenopausal women, only partially explained by weight and weight change. This study is registered with clinicaltrials.gov identifier: NCT00000611.

Comparison of the Ketogenic Ratio of Macronutrients With the Low-Carbohydrate Diet Score and Their Association With Risk of Type 2 Diabetes in Postmenopausal Women: A Secondary Analysis of the Women's Health Initiative.

BACKGROUND: Previous attempts to identify low-carbohydrate diets (LCDs) in epidemiological studies relied on the LCD Score, which is unable to identify ketogenic dieters. Ketogenic ratios of macronutrients are clinical equations proposed to predict ketogenic diets; however, their utility in epidemiological studies is unknown. OBJECTIVE: To determine the number of participants consuming a ketogenic diet, compare ketogenic ratios to the LCD Score, and evaluate their association with type 2 diabetes mellitus (T2DM). DESIGN: Secondary analysis of the Women's Health Initiative with 17.9 ± 6.03 years of follow-up. Baseline food frequency questionnaires were used to calculate the ketogenic ratio as follows: (0.9 × grams fat + 0.46 × grams protein) / (0.1 × grams fat + 0.58 × grams protein + grams net carbohydrate), a value ≥1.5 is the minimum threshold for a ketogenic diet. PARTICIPANTS/SETTING: One hundred twenty-five nine hundred eighty-two postmenopausal women without diabetes (aged 50 to 79 years) enrolled in the multicenter Women's Health Initiative observational study and clinical trials were included. MAIN OUTCOME MEASURES: Risk of self-reported incident T2DM. STATISTICAL ANALYSES PERFORMED: Cox proportional hazards models, adjusted for age, race, ethnicity, education, income, health insurance, relationship status, geographic region, Women's Health Initiative study component, female hormone use, smoking status, alcohol use, recreational physical activity, total energy intake, diet quality, body mass index, hyperlipidemia, and hypertension, were used to compare hazard ratios and 95% CIs for T2DM among quintiles of the ketogenic ratio. RESULTS: A total of 18,775 incident cases of T2DM occurred. The median ketogenic ratio was 0.35 (interquartile range 0.28 to 0.42) and 15 individuals (0.01%) exceeded the threshold for a ketogenic diet. Higher ketogenic ratio quintiles were associated with increased risk of T2DM in a dose-dependent manner. Comparing extreme quintiles of the ketogenic ratio, the hazard ratio for diabetes was 1.24 (95% CI 1.18 to 1.31; Ptrend < 0.001) in fully adjusted models. Similarly, comparing extreme quintiles, the hazard ratio for diabetes was 1.36 (95% CI 1.29 to 1.43; Ptrend < 0.001) for the LCD Score and 1.13 (95% CI 1.07 to 1.19; Ptrend < 0.001) for the simplified ketogenic ratio in fully adjusted models. CONCLUSIONS: Increasing ketogenic ratio values are associated with increased risk of T2DM and align well with LCD Scores; however, too few participants consumed a ketogenic diet to determine its association with T2DM.

Chocolate Consumption in Relation to All-Cause and Cause-Specific Mortality in Women: The Women's Health Initiative.

BACKGROUND: Chocolate contains both potentially harmful components (ie, stearic acid and added sugar) and beneficial components (ie, phenolics and flavonoids). Despite its popularity, the long-term health effects of chocolate consumption remain unclear. OBJECTIVE: The aim of this study was to examine the association of chocolate consumption with all-cause and cause-specific mortality. DESIGN: This was a prospective cohort study. PARTICIPANTS/SETTING: This study included 84,709 postmenopausal women free of cardiovascular disease (CVD) and cancer at baseline in the observational study and clinical trials control arms of the prospective Women's Health Initiative cohort who were enrolled during 1993 through 1998. These women were followed through March 2018. MAIN OUTCOME MEASURES: The outcomes included all-cause mortality and cause-specific mortality from CVD, cancer, and dementia. STATISTICAL ANALYSES PERFORMED: Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) of all-cause mortality and cause-specific mortality. RESULTS: During 1,608,856 person-years of follow-up (mean [SD] of 19.0 [4.2] years), 25,388 deaths occurred, including 7,069 deaths from CVD, 7,030 deaths from cancer, and 3,279 deaths from dementia. After adjustment for a variety of covariates, compared with no chocolate consumption, the HRs (95% CI) for all-cause mortality were 0.95 (0.92 to 0.98), 0.93 (0.89 to 0.96), 0.97 (0.90 to 1.04), and 0.90 (0.84 to 0.97) for <1 serving/wk, 1 to 3 servings/wk, 4 to 6 servings/wk, and ≥1 serving/d of chocolate consumption, respectively (P for trend = .02). For CVD mortality, compared with no chocolate consumption, the HRs (95% CI) were 0.96 (0.91 to 1.01), 0.88 (0.82 to 0.95), 1.06 (0.93 to 1.21), and 0.92 (0.80 to 1.05) for <1 serving/wk, 1 to 3servings/wk, 4 to 6 servings/wk, and ≥1 serving/d of chocolate consumption, respectively (P for trend =.45). For dementia mortality, compared with no chocolate consumption, the HRs (95% CI) were 0.91 (0.84 to 0.99), 0.89 (0.80 to 0.99), 0.97 (0.79 to 1.18), and 0.97 (0.80 to 1.18) for <1 serving/wk, 1 to 3 servings/wk, 4-6 servings/wk, and ≥1 serving/d of chocolate consumption, respectively (P for trend = .95). Chocolate consumption was not associated with cancer mortality. CONCLUSIONS: The results suggest a modest inverse association of chocolate consumption with mortality from all causes, CVD, or dementia, specifically for moderate chocolate consumption of 1 to 3 servings/wk.

Changes in Dietary Intake of Methionine, Folate/Folic Acid and Vitamin B12 and Survival in Postmenopausal Women with Breast Cancer: A Prospective Cohort Study.

BACKGROUND: Previous experimental studies showed that limiting methionine in the diet of animals or in cell culture media suppresses mammary cancer cell proliferation or metastasis. However, no previous study has investigated the associations of changes in methionine intake with survival among breast cancer survivors. We aimed to examine the association between changes in dietary intake of methionine, folate/folic acid, and vitamin B12 from before to after diagnosis of breast cancer, and mortality among breast cancer survivors. METHODS: We included 1553 postmenopausal women from the Women's Health Initiative who were diagnosed with invasive breast cancer and completed a food frequency questionnaire both before and after breast cancer diagnosis. Multivariable Cox proportional hazards regression models were used to estimate adjusted hazard ratios (HRs) and 95% confidence (CIs) of all-cause and breast cancer mortality associated with changes in methionine intake and changes in folate/folic acid and vitamin B12 intake. RESULTS: Relative to pre-diagnosis, 28% of women decreased methionine intake by ≥20%, 30% of women increased methionine intake by ≥20%, and 42% of women had a relatively stable methionine intake (±19.9%) following breast cancer diagnosis. During a mean 16.1 years of follow up, there were 772 deaths in total, including 195 deaths from breast cancer. Compared to women with relatively stable methionine intake, women with decreased methionine intake had lower risks of all-cause (HR 0.78, 95% CI 0.62-0.97) and breast cancer mortality (HR 0.58, 95% CI 0.37-0.91) in fully adjusted models. In contrast, increased methionine intake or changes in folate/folic acid or vitamin B12 intake were not associated with all-cause or breast cancer mortality. CONCLUSIONS: Among breast cancer survivors, decreased methionine intake after breast cancer diagnosis was associated with lower risk of all-cause and breast cancer mortality.

Large-scale population disappearances and cycling in the white-lipped peccary, a tropical forest mammal.

Many vertebrate species undergo population fluctuations that may be random or regularly cyclic in nature. Vertebrate population cycles in northern latitudes are driven by both endogenous and exogenous factors. Suggested causes of mysterious disappearances documented for populations of the Neotropical, herd-forming, white-lipped peccary (Tayassu pecari, henceforth "WLP") include large-scale movements, overhunting, extreme floods, or disease outbreaks. By analyzing 43 disappearance events across the Neotropics and 88 years of commercial and subsistence harvest data for the Amazon, we show that WLP disappearances are widespread and occur regularly and at large spatiotemporal scales throughout the species' range. We present evidence that the disappearances represent 7-12-year troughs in 20-30-year WLP population cycles occurring synchronously at regional and perhaps continent-wide spatial scales as large as 10,000-5 million km2. This may represent the first documented case of natural population cyclicity in a Neotropical mammal. Because WLP populations often increase dramatically prior to a disappearance, we posit that their population cycles result from over-compensatory, density-dependent mortality. Our data also suggest that the increase phase of a WLP cycle is partly dependent on recolonization from proximal, unfragmented and undisturbed forests. This highlights the importance of very large, continuous natural areas that enable source-sink population dynamics and ensure re-colonization and local population persistence in time and space.

The Role of Incarceration as a Risk Factor for Cognitive Impairment.

OBJECTIVES: The objective of this study was to understand disparities in cognitive impairment between middle-aged formerly incarcerated (FI) and nonincarcerated individuals. METHODS: The 1979 National Longitudinal Survey of Youth is a nationally representative longitudinal data set containing information on incarceration, cognitive functioning, and other health conditions. Using a modified version of the Telephone Interview for Cognitive Status (TICS-m), adapted from the Health and Retirement Study, we analyzed the association between incarceration and cognitive impairment, cognitive impairment-not dementia and dementia. Multivariable regression models were estimated, including prior incarceration status and covariates associated with incarceration and cognitive functioning. RESULTS: FI individuals had lower unadjusted scores on TICS-m (-2.5, p < .001) and had significantly greater unadjusted odds ratios (OR) for scoring in the cognitive impairment (OR = 2.4, p < .001) and dementia (OR = 2.7, p < .001) range. Differences were largely explained by a combination of risk factors associated with incarceration and cognition. Education and premorbid cognition (measured by Armed Forces Qualification Test) separately and completely explained differences in the odds of dementia. Regardless of incarceration status, Blacks and Hispanics had significantly greater odds of cognitive impairment and dementia relative to Whites, holding other factors constant. DISCUSSION: The association between prior incarceration and cognitive impairment in middle age was largely explained by differences in educational attainment and premorbid cognitive functioning, supporting the cognitive reserve hypothesis. Greater prevalence of cognitive impairment and dementia among the FI could create challenges and should be considered in reentry planning. Structural and institutional factors should be considered when addressing health disparities in Alzheimer's Disease and Related Dementias.