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We previously showed that a food-based empirical dietary inflammatory pattern (EDIP) score is associated with circulating inflammatory biomarkers. Metabolomic profiling of inflammatory diets may therefore provide insights on mechanisms contributing to disease etiology and prognosis. We aimed to elucidate metabolites associated with inflammatory diets among postmenopausal women, utilizing a robust study design that incorporates independent discovery and validation datasets. This baseline cross-sectional investigation evaluated associations between continuous EDIP scores calculated from food frequency questionnaires and 448 log-transformed plasma metabolites as outcomes in multivariable-adjusted linear regression analyses. Metabolites were measured with liquid chromatography tandem mass spectroscopy. Metabolite discovery was conducted among 1109 Women's Health Initiative (WHI) Hormone Therapy trial participants and results were replicated in an independent dataset of 810 WHI Observational Study participants. Secondary analyses were stratified by standard body mass index (BMI, kg/m2) categories. In discovery and replication datasets statistical significance was based on false-discovery rate adjusted P < 0.05. After adjusting for energy intake, BMI, physical activity, and other confounding variables, 23 metabolites were significantly associated with EDIP score in the discovery dataset. Of these, the following ten were replicated: trigonelline, caffeine, acethylamino-6-amino-3-methyluracil, 7-methylxanthine, 1,7-dimethyluric acid, 3-methylxanthine, C18:3CE, glycine, associated with lower dietary inflammatory potential; whereas C52:3 triacylglycerol and linoleate associated with higher dietary inflammatory potential. Four of the ten were associated [glycine (inversely), caffeine, 1,7-dimethyluric acid, C52:3 triacylglycerol, (positively)], with C-reactive protein levels. In secondary analyses, associations showed differences by BMI category. Four metabolites, related to coffee/caffeine metabolism were inversely associated among normal weight women, and 83 metabolites associated with EDIP among overweight/obese women, including 40 (48%) that were also associated with C-reactive protein. Metabolites associated with coffee/caffeine and lipid metabolism may reflect the inflammatory potential of diet. Potential differences by BMI and the linkage to disease outcomes, require further study. • Diet may influence disease risk and progression through inflammation. • The specific mechanisms involved are not fully understood. • Metabolomic profiling of inflammatory diets may therefore provide insights. • We identified and replicated 10 metabolites associated with diet-related inflammation. • Metabolites associated with lipid metabolism may reflect diet-related inflammation. [ABSTRACT FROM AUTHOR]

Objectives: While sleep is critical for good health, it remains a major public health concern because millions of individuals do not obtain a sufficient amount of sleep at night to reap proper health benefits. When examining factors that contribute to deleterious sleep outcomes, few researchers to date have examined the physical and social environments together. Study design: This article is an analytical essay. Methods: In the present study, 18 empirical articles on environmental factors that promote sleep loss were analyzed and synthesized according to the study type, exposure measures, outcome measures, methodology, and findings. Results: Data from the literature demonstrate that neighborhood airplane, roadway, and rail noise pollution; air pollution from ozone and particulate matter (PM10); and, to some extent, ambient light, interfere with residents' ability to fall asleep, stay asleep, and wake feeling rested. There is also some evidence that neighborhood green space, walkability, safety, built environment, and other social characteristics, such as neighborhood disorder and ability to trust one's neighbors, dramatically impact residents' sleep. Conclusions: This article provides a critical assessment of the multidimensional relationship between neighborhood physical and social characteristics and sleep, addresses major methodological concerns that limit current empirical knowledge, and suggests steps to shape future research. [ABSTRACT FROM AUTHOR]

Background: The empirical dietary inflammatory pattern (EDIP) score has been associated with concentrations of circulating inflammatory biomarkers in European Americans.Objective: We used the EDIP score, a weighted sum of 18 food groups that characterizes dietary inflammatory potential based on circulating concentrations of inflammatory biomarkers, to test the hypothesis that a pro-inflammatory dietary pattern is associated with inflammatory biomarker concentrations in a US multi-ethnic population.Methods: In this cross-sectional study, we calculated EDIP scores using baseline food frequency questionnaire data from 31,472 women, aged 50-79 y, in the Women's Health Initiative observational study and clinical trials. Circulating biomarkers outcomes at baseline were: C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor (TNF)-α, TNF receptor (TNFR) 1 and 2, and adiponectin. We used multivariable-adjusted linear regression analyses to estimate absolute concentrations and relative differences in biomarker concentrations, overall and in subgroups of race/ethnicity and BMI (body mass index) categories.Results: Independent of energy intake, BMI, physical activity, and other potential confounding variables, higher EDIP scores were significantly associated with higher (lower for adiponectin) absolute concentrations of all 6 biomarkers. On the relative scale, the percentage of difference in the concentration of biomarkers, among women in the highest compared to the lowest EDIP quintile, was: CRP, +13% (P-trend < 0.0001); IL-6, +15% (P-trend < 0.0001); TNF-α, +7% (P-trend = 0.0007); TNFR1, +4% (P-trend = 0.0009); TNFR2, +5% (P-trend < 0.0001); and adiponectin, -13% (P-trend <0.0001). These associations differed by racial/ethnic groups and by BMI categories. Whereas the absolute biomarker concentrations were lower among European-American women and among normal-weight women, the associations with diet were stronger than among women of African-American or Hispanic/Latino origin and among overweight and obese women.Conclusions: Findings demonstrate the successful replication of an empirical hypothesis-oriented a posteriori dietary pattern score in a multi-ethnic population of postmenopausal women, with subgroup differences by race/ethnicity and body weight. Future research needs to apply the score in non-US populations. [ABSTRACT FROM AUTHOR]

Objective: Identify depression symptoms during active late-life depression (LLD) that predict conversion to dementia.Methods: The authors followed a cohort of 290 participants from the Neurocognitive Outcomes of Depression in the Elderly study. All participants were actively depressed and cognitively normal at enrollment. Depression symptom factors were derived from prior factor analysis: anhedonia and sadness, suicidality and guilt, appetite and weight loss, sleep disturbance, and anxiety and tension. Cox regression analysis modeled time to Alzheimer disease (AD) and non-AD dementia onset on depression symptom factors, along with age, education, sex, and race. Significant dementia predictors were tested for interaction with age at depression onset.Results: Higher scores on the appetite and weight loss symptom factor were associated with an increased hazard of both AD and non-AD dementia. This factor was moderated by age at first depression onset, such that higher scores were associated with higher risk of non-AD dementia when depression first occurred earlier in life. Other depression symptom factors and overall depression severity were not related to risk of AD or non-AD dementia.Conclusion: Results suggest greater appetite/weight loss symptoms in active episodes of LLD are associated with increased likelihood of AD and non-AD dementia, but possibly via different pathways moderated by age at first depression onset. Results may help clinicians identify individuals with LLD at higher risk of developing AD and non-AD dementia and design interventions that reduce this risk. [ABSTRACT FROM AUTHOR]

The article makes use of the data from the National Alzheimer Disease Coordinating Center (NACC) to identify subtypes of cognitively normal adults with various cognition patterns, which may imply later Alzheimer disease (AD) or dementia onset. Findings discussed include the results of the exploratory factor analysis (EFA) performed on the first half of the sample, the latent profile analysis (LPA) done using the CFA factor scores, baseline age and sex, and the predictors of profile membership.

Objectives: 1) To report rates of neuropsychiatric symptoms (NPS) in cognitive impairment, no dementia (CIND). 2) To compare the 30-day prevalence of NPS in CIND with that in dementia and cognitively normal individuals. 3) To compare the prevalence of NPS in amnestic MCI (aMCI) with other predementia syndromes. Design: Comparison of prevalence proportions among several defined groups. Setting: Population-based study. Participants: A subsample of the permanent residents of Cache County, Utah, aged 65 years or older in January 1995 (N = 5092) and who had completed clinical assessments and had an informant-completed Neuropsychiatric Inventory. Measurements: Chi-square statistics, tests for trend, and logistic regression models were used to analyze the three objectives listed earlier. Results: The most prevalent NPS in those with CIND were depression (16.9%), irritability (9.8%), nighttime behaviors (7.6%), apathy (6.9%), and anxiety (5.4%). Trend analyses confirmed that the CIND group had NPS prevalence rates that fell between the normal and dementia groups for most NPS. Logistic regression models showed no significant difference between aMCI and other CIND participants in the prevalence of any NPS (lowest p: 0.316). Conclusions: These data confirm the relatively high prevalence of NPS in CIND reported by other studies, especially for affective symptoms. No differences in NPS prevalence were found between aMCI and other types of CIND. [ABSTRACT FROM AUTHOR]

: Background and objectivesTo avoid costly evaluation of healthy individuals, efficient methods of screening for incident dementia must combine adequate sensitivity and high specificity. Two-stage screening may offer improvements over single-stage methods. We therefore investigated a two-stage screening protocol for incident dementia among 3,308 elderly.: MethodsWe administered the Modified Mini-Mental-State (3MS) or, rarely, Jorm''s IQCODE, to a validation sample of 441 high-risk respondents. Informants then completed the Dementia Questionnaire (DQ). Finally, all 441 sample members underwent physical, neurologic, and neuropsychologic assessment. We studied the sensitivity and specificity of the 3MS/IQCODE and DQ using Receiver-Operating Characteristic analyses.: ResultsA 3MS cut point of 82/83 (of 100) yielded sensitivity and specificity of 91.5 and 90.1%. With 3MS scores of &les;82, a DQ cut point of 2/3 (of five) yielded conditional sensitivity and specificity of 90.2 and 55.3%. Combining these instruments yielded sensitivity and specificity of 82.5 and 95.6%. Age stratification and use of longitudinal decline score criteria did not materially improve these figures.: ConclusionsThe improved specificity of the two-stage approach offers economies that are attractive, particularly if sensitivity can be enhanced, for example, by examination of a high-risk validation sample. [Copyright &y& Elsevier]

Clonal hematopoiesis of indeterminate potential (CHIP), the expansion of leukemogenic mutations in white blood cells, has been associated with increased risk of atherosclerotic cardiovascular diseases, cancer, and mortality. We examined the relationship between individual- and neighborhood-level socioeconomic status (SES) and CHIP and evaluated effect modification by interpersonal and intrapersonal resources. The study population included 10,799 postmenopausal women from the Women's Health Initiative without hematologic malignancy or antineoplastic medication use. Individual- and neighborhood (Census tract)-level SES were assessed across several domains including education, income, and occupation, and a neighborhood-level SES summary z -score, which captures multiple dimensions of SES, was generated. Interpersonal and intrapersonal resources were self-reports. CHIP was ascertained based on a prespecified list of leukemogenic driver mutations. Weighted logistic regression models adjusted for covariates were used to estimate risk of CHIP as an odds ratio (OR) and 95% confidence interval (95% CI). The interval-scale neighborhood-level SES summary z -score was associated with a 3% increased risk of CHIP: OR (95% CI) = 1.03 (1.00–1.05), p =.038. Optimism significantly modified that estimate, such that among women with low/medium and high levels of optimism, the corresponding ORs (95% CIs) were 1.03 (1.02–1.04) and 0.95 (0.94–0.96), p Interaction <.001. Our findings suggest that reduced risk of somatic mutation may represent a biological pathway by which optimism protects contextually advantaged but at-risk women against age-related chronic disease and highlight potential benefits of long-term, positive psychological interventions. [ABSTRACT FROM AUTHOR]

The WHI (Women's Health Initiative) enrolled 161,808 racially and ethnically diverse postmenopausal women, ages 50-79 years, from 1993 to 1998 at 40 clinical centers across the United States. In its clinical trial component, WHI evaluated 3 randomized interventions (menopausal hormone therapy; diet modification; and calcium/vitamin D supplementation) for the primary prevention of major chronic diseases, including cardiovascular disease, in older women. In the WHI observational study, numerous clinical, behavioral, and social factors have been evaluated as predictors of incident chronic disease and mortality. Although the original interventions have been completed, the WHI data and biomarker resources continue to be leveraged and expanded through ancillary studies to yield novel insights regarding cardiovascular disease prevention and healthy aging in women. [ABSTRACT FROM AUTHOR]

Aims: To assess whether there is an opportune window when intensive lifestyle intervention (ILI) benefits cognitive function.Methods: Standardized cognitive assessments were collected following ≥8 years of either ILI or a control condition of diabetes support and education (DSE) in 3708 individuals, ages 45-76 years at enrollment, with type 2 diabetes and overweight or obesity. Frailty index (FI) scores were used to group individuals at baseline into tertiles according to their age-related health status. Linear models were used to describe intervention adherence and cognitive function, with interaction terms to examine the consistency of relationships among tertiles.Results: Worse baseline FI scores were associated with poorer subsequent performance in tests of attention, processing speed, and executive function. No differences in any measure of cognitive function were observed between intervention groups within any FI tertile (all p > 0.10). Among individuals with worse baseline FI scores, weight gain was associated with poorer global cognitive function among participants assigned to DSE. There was no association between weight changes and cognitive function among participants assigned to ILI.Conclusions: Among adults with type 2 diabetes and overweight/obesity, we found no evidence that there is a window of opportunity based on FI when ILI benefits cognitive function. [ABSTRACT FROM AUTHOR]

Variants associated with modulation of c-reactive protein (CRP) and plasma lipids have been investigated for polygenic overlap with Alzheimer's disease risk variants. We examined pleiotropic genetic effects on cognitive impairment conditioned on genetic variants (SNPs) associated with systemic inflammation as measured by CRP and with plasma lipids using data from the Health and Retirement Study. SNP enrichment was observed for cognitive impairment conditioned on the secondary phenotypes of plasma CRP and lipids. Fold enrichment of 100%–800% was observed for increasingly stringent p -value thresholds for SNPs associated with cognitive impairment conditional on plasma CRP, 80%–800% for low-density lipoprotein, and 80%–600% for total cholesterol. Significant associations (false discovery rate Q ≤ 0.05) between cognitive impairment, conditional with either CRP, low-density lipoprotein, or total cholesterol, were found for the locus on chromosome 19 that contains the APOE, TOMM40, APOC1, and PVRL2 genes. Relative numbers of significant SNPs in each of the genes differed by the conditional associations with the secondary phenotypes. Biological interpretation of both the genetic pleiotropy results and the individual genome-wide association results showed that the variants and proximal genes identified are involved in multiple pathological processes including cholesterol metabolism, inflammation, and mitochondrial transport. These findings are potentially important for Alzheimer's disease risk prediction and development of novel therapeutic approaches. • We examined pleiotropic genetic effects on cognitive impairment (CI) with HRS data. • We tested for SNP enrichment for CI conditional with plasma CRP and lipid levels. • SNP enrichment was observed for CI conditioned on CRP levels. LDL levels and total cholesterol levels. • Significant associations between cognitive impairment, conditional with either CRP, LDL or TC were found for the locus on chromosome 19 that contains the APOE, TOMM40, APOC1, PVRL2 genes. • Variants and proximal genes identified are involved in multiple pathological processes including cholesterol metabolism, inflammation and mitochondrial transport. [ABSTRACT FROM AUTHOR]

Aims: To assess associations that endogenous estradiol and testosterone levels have with cognitive function in older adults with Type 2 diabetes mellitus (T2DM).Methods: We use data from the Look AHEAD clinical trial of behavioral weight loss. Endogenous estradiol and total testosterone levels were determined using stored serum from 996 individuals, mean age 69 years, at two times (averaging 4 years apart) during years 8-18 of follow-up. One to four standardized assessments of attention, executive function, memory, and verbal fluency were collected during this follow-up. Mixed effects models and multiple imputation were used to assess associations that estradiol and total testosterone levels had with body mass index and cognitive function.Results: Estradiol levels were not associated with cognitive function in either sex. Total testosterone levels were not associated with cognitive function in women, but greater total testosterone levels were associated with better verbal fluency in men (p < 0.001), most strongly among those carrying the APOE-e4 allele (interaction p = 0.02). The weight loss intervention left a legacy of relatively lower cognitive functioning among women, which was not mediated by current levels of sex hormones.Conclusions: Behavioral weight loss intervention does not affect cognitive functioning through mechanisms related to estradiol or testosterone.Clinicaltrials: gov Identifier: NCT00017953. [ABSTRACT FROM AUTHOR]