Dataset Information

A candidate gene study of risk for dementia in older, postmenopausal women: Results from the Women's Health Initiative Memory Study.

ABSTRACT: OBJECTIVE:While a number of single nucleotide polymorphisms (SNPs) associated with Alzheimer's disease (AD) or cognitive impairment have been identified, independent replications remain the only way to validate proposed signals. We investigated SNPs in candidate genes associated with either cognitive impairment or AD pathogenesis and their relationships with probable dementia (PD) in the Women's Health Initiative Memory Study (WHIMS). METHODS:We analyzed 96 SNPs across five genes (APOE/TOMM40, BDNF, COMT, SORL1, and KIBRA) in 2857 women (ages ?65) from the WHIMS randomized trials of hormone therapy using a custom Illumina GoldenGate assay; 19% of the sample were MCI (N = 165) or PD (N = 387), and the remaining 81% were free of cognitive impairment. SNP associations were evaluated for PD in non-Hispanic whites adjusting for age and HT using logistic regression under an additive genetic model. RESULTS:One SNP (rs157582), located in the TOMM40 gene nearby APOE, was associated with the PD phenotype based on a P value accounting for multiple comparisons. An additional 12 SNPs were associated with the PD phenotype at P ? 0.05 (APOE: rs405509, rs439401; TOMM40: rs8106922, and KIBRA: rs4320284, rs11740112, rs10040267, rs13171394, rs6555802, rs2241368, rs244904, rs6555805, and rs10475878). Results of the sensitivity analyes excluding MCI were similar, with addition of COMT rs737865 and BDNF rs1491850 (P ? 0.05). CONCLUSIONS:Our results in older women provide supporting evidence that the APOE/TOMM40 genes confer dementia risk and extend these findings to COMT, BDNF, and KIBRA. Our findings may lead to a better understanding of the role these genes play in cognition and cognitive impairment.

SUBMITTER: Driscoll I

PROVIDER: S-EPMC6608707 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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A candidate gene study of risk for dementia in older, postmenopausal women: Results from the Women's Health Initiative Memory Study.

Driscoll Ira I Snively Beverly M BM Espeland Mark A MA Shumaker Sally A SA Rapp Stephen R SR Goveas Joseph S JS Casanova Ramon L RL Wactawski-Wende Jean J Manson JoAnn E JE Rossom Rebecca R Brooks Janet J Hernandez Dena G DG Singleton Andrew B AB Resnick Susan M SM

International journal of geriatric psychiatry 20190307 5

<h4>Objective</h4>While a number of single nucleotide polymorphisms (SNPs) associated with Alzheimer's disease (AD) or cognitive impairment have been identified, independent replications remain the only way to validate proposed signals. We investigated SNPs in candidate genes associated with either cognitive impairment or AD pathogenesis and their relationships with probable dementia (PD) in the Women's Health Initiative Memory Study (WHIMS).<h4>Methods</h4>We analyzed 96 SNPs across five genes ...[more]

PMID: 30706571

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Project description:IMPORTANCE:Considerable efforts have been undertaken to relate single nutrients to bone health. To this point, results are inconsistent. Suboptimal single nutrient intake does not occur in isolation but rather reflects a poor diet quality. OBJECTIVE:To assess the association between adherence to a diet quality index constructed on the basis of dietary recommendations or existing healthy dietary patterns and fractures in postmenopausal women. DESIGN, SETTING, AND PARTICIPANTS:Post hoc analysis was conducted of longitudinal data from 40 clinical centers throughout the United States included in the Women's Health Initiative (WHI) observational study. Participants in the prospective cohort included 93?676 women who were eligible for the WHI if they were aged 50 to 79 years. Recruitment was conducted from October 1, 1993, to December 31, 1998, with the study ending August 29, 2014. The WHI food frequency questionnaire was used to derive nutrient and food intake at baseline. Diet quality and adherence were assessed by scores on the alternate Mediterranean Diet (aMED), a 9-category measure of adherence to a Mediterranean dietary pattern; the Healthy Eating Index 2010 (HEI-2010), a 100-point measure of 12 food components; the 11-item Alternate Healthy Eating Index 2010 (AHEI-2010); or the 8-component Dietary Approaches to Stop Hypertension (DASH) diet score. MAIN OUTCOMES AND MEASURES:Outcome measures included incident total and hip fractures. Hazard ratios (HRs) by quintiles of dietary index scores were estimated using Cox proportional hazards regression analyses. RESULTS:Of the 93?676 participants, 90?014 were included in the analysis (mean [SD] age, 63.6 [7.4]) years. During a median follow-up time of 15.9 years, there were 2121 cases of hip fractures and 28?718 cases of total fractures. Women scoring in the highest quintile (Q5) of the aMED index had a lower risk for hip fractures (HR, 0.80; 95% CI, 0.66-0.97), with an absolute risk reduction of 0.29% and a number needed to treat of 342 (95% CI, 249-502). No association between the aMED score and total fractures was observed (Q5 HR, 1.01; 95% CI, 0.95-1.07). Higher HEI-2010 or DASH scores tended to be inversely related to hip fracture risk, but the results were nonsignificant (Q5 HR, 0.87; 95% CI, 0.75-1.02; and Q5 HR, 0.89; 95% CI, 0.75-1.06, respectively). The AHEI-2010 score was associated with neither hip nor total fractures. CONCLUSIONS AND RELEVANCE:Higher adherence to a Mediterranean diet is associated with a lower risk for hip fractures. These results support that a healthy dietary pattern may play a role in maintaining bone health in postmenopausal women.

Project description:BACKGROUND:There is a paucity of research on prehypertension and incident hypertension among postmenopausal Hispanic women. The overall objective is to determine the multiple risk factors associated with the prevalence of hypertension status at baseline and incident hypertension at year 3 in postmenopausal Hispanic women. METHODS:For the analyses in this paper, we included a total of 4,680 Hispanic women who participated in the Women's Health Initiative (WHI), a randomized clinical trial and observational study, at baseline (1994-1998) and at third-year follow-up and for whom blood pressure was measured at year 3 (n = 3,848). Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of hypertension status, defined as systolic blood pressure ?140 mm Hg and/or diastolic blood pressure ?90 mm Hg, to assess the odds of incident hypertension at year 3 of follow-up in association with the factors included in the baseline models. RESULTS:At year 3 of follow-up, 27.3% of Hispanic women who were normotensive at baseline had progressed to prehypertension, and 9.0% had become hypertensive. Among the prehypertensive participants at baseline, 30.4% had progressed to hypertension. Compared with normotensive Hispanic women, hypertensive participants had a higher number of cardiovascular risk factors: body mass index ?30 kg/m(2) (OR = 3.76; 95% CI = 3.01-4.71), a family history of diabetes, stroke, and/or myocardial infarction (OR = 1.12; 95% CI 1.03-1.23), treated hypercholesterolemia (OR = 1.57; 95% CI = 1.23-1.99), treated diabetes (OR = 2.04; 95% CI = 1.40-2.97), and a history of cardiovascular disease (OR = 2.04; 95% CI = 1.58-2.64). CONCLUSIONS:Hispanic women seem to experience an increased risk of incident hypertension in later adulthood. On a practical level, recommendations for preventive care and population-wide adoption of health behaviors, such as community-focused campaigns to engage in physical activity, may contribute to reductions in hypertension risk factors. CLINICAL TRIALS REGISTRATION:Trial Number NCT00000611.

Project description:Study questionWhat is the association between reproductive health history (e.g. age at menarche, menopause, reproductive lifespan) with abdominal adiposity in postmenopausal women?Summary answerHigher visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) tissue levels were observed among women with earlier menarche, earlier menopause, and greater parity.What is known alreadyPostmenopausal women are predisposed to accumulation of VAT and SAT. Reproductive health variables are known predictors of overall obesity status in women, defined by BMI.Study design, size, durationThis study is a secondary analysis of data collected from the baseline visit of the Women's Health Initiative (WHI). The WHI is a large prospective study of postmenopausal women, including both a randomized trial and observational study. There were 10 184 women included in this analysis.Participants/materials, setting, methodsData were collected from a reproductive health history questionnaire, dual-energy x-ray absorptiometry scans, and anthropometric measures at WHI baseline. Reproductive history was measured via self-report, and included age at menarche, variables related to pregnancy, and age at menopause. Reproductive lifespan was calculated as age at menopause minus age at menarche. Statistical analyses included descriptive analyses and multivariable linear regression models to examine the association between reproductive history with VAT, SAT, total body fat, and BMI.Main results and the role of chanceWomen who reported early menarche (<10 years) or early menopause (<40 years) had the highest levels of VAT. Adjusted multivariable linear regression results demonstrate women who experienced menarche >15 years had 23 cm2 less VAT (95% CI: -31.4, -14.4) and 47 cm2 less SAT (95% CI: -61.8, -33.4) than women who experienced menarche at age 10 years or earlier. A similar pattern was observed for age at menopause: compared to women who experienced menopause <40 years, menopause at 50-55 years was associated with 19.3 cm2 (95% CI: -25.4, -13.3) less VAT and 27.4 cm2 (-29.6, 10.3) less SAT. High parity (>3 pregnancies) was also associated with VAT and SAT. For example, adjusted beta coefficients for VAT were 8.36 (4.33, 12.4) and 17.9 (12.6, 23.2) comparing three to four pregnancies with the referent, one to two pregnancies.Limitations, reasons for cautionThe WHI reproductive health history questionnaire may be subject to poor recall owing to a long look-back window. Residual confounding may be present given lack of data on early life characteristics, such as maternal and pre-menarche characteristics.Wider implications of the findingsThis study contributes to our understanding of reproductive lifespan, including menarche and menopause, as an important predictor of late-life adiposity in women. Reproductive health has also been recognized as a sentinel marker for chronic disease in late life. Given established links between adiposity and cardiometabolic outcomes, this research has implications for future research, clinical practice, and public health policy that makes use of reproductive health history as an opportunity for chronic disease prevention.Study funding/competing interest(s)HRB and AOO are supported by the National Institute of Health National Institute of Aging (R01AG055018-04). JWB reports royalties from 'ACSM'S Body Composition Assessment Book' and consulting fees from the WHI. The remaining authors have no competing interests to declare.Trial registration numberN/A.

Project description:BackgroundProlonged sitting and lower levels of physical activity have been associated with increased levels of parent oestrogens (oestrone and oestradiol), the key hormones in female cancers, in postmenopausal women. However, it is unknown whether sitting and physical activity are associated with circulating oestrogen metabolite levels.MethodsAmong 1804 postmenopausal women enrolled in the Women's Health Initiative Observational Study, 15 serum oestrogens/oestrogen metabolites were quantified using liquid chromatography-tandem mass spectrometry. Physical activity and sitting were self-reported via questionnaire. Using baseline, cross-sectional data, geometric means (GM) of oestrogens/oestrogen metabolites (pmol?l-1) were estimated using inverse probability weighted linear regression, adjusting for potential confounders and stratified on menopausal hormone therapy (MHT) use.ResultsLonger time spent sitting (?10 vs ?5h per day) was associated with higher levels of unconjugated oestrone, independent of moderate- to vigorous-intensity physical activity and body mass index, among both never/former (GM=70.6 vs 57.7) and current MHT users (GM=242 vs 179) (P-trend ?0.03). Among never/former MHT users, sitting (?10 vs ?5h per day) was positively associated with 2-methoxyestradiol (GM=16.4 vs 14.4) and 4-methoxyestradiol (GM=2.36 vs 1.98) (P-trend ?0.04), independent of parent oestrogens. Inverse associations between moderate- to vigorous-intensity physical activity (?15 vs 0 metabolic equivalent task-hours per week) and parent oestrogens were found as expected. After adjustment for parent oestrogens, physical activity was not associated with oestrogen metabolites.ConclusionsOur data suggest that prolonged sitting and lower moderate- to vigorous-intensity physical activity are associated with higher levels of postmenopausal oestrogens/oestrogen metabolites, the oestrogen metabolism patterns that have previously been associated with higher endometrial and breast cancer risk.

Dataset Information

A candidate gene study of risk for dementia in older, postmenopausal women: Results from the Women's Health Initiative Memory Study.

Publications

A candidate gene study of risk for dementia in older, postmenopausal women: Results from the Women's Health Initiative Memory Study.

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