Biomarkers.

Background: There is an urgent need to identify novel, accessible and affordable strategies to prevent cognitive decline and progression in the Alzheimer disease and related dementias (ADRD) continuum. Vitamin D3 and marine omega-3 fatty acids (omega-3s) supplements show promise for cognitive protection, with potential variations in their effects by sex or race. However, to date, no randomized clinical trials (RCTs) have tested their impact on emerging plasma-based biomarkers with potential utility to predict ADRD pathogenesis.

Developing Topics.

Background: Older women have a higher prevalence of Alzheimer's disease relative to comparably aged men. Although the biological mechanisms driving this sex difference remain elusive, emerging data suggest that longevity, APOEε4, inflammation, and blood glucose levels may play roles. Our objective was to examine the associations of APOEε4, high sensitivity-C-reactive protein (hs-CRP), and fasting blood glucose levels with cognitive changes over time among women enrolled in two ancillary studies of the Women's Health Initiative (WHI).

Coffee drinking timing and mortality in US adults.

Background And Aims: To identify the patterns of coffee drinking timing in the US population and evaluate their associations with all-cause and cause-specific mortality.

Methods: This study included 40 725 adults from the National Health and Nutrition Examination Survey 1999-2018 who had complete information on dietary data and 1463 adults from the Women's and Men's Lifestyle Validation Study who had complete data on 7-day dietary record. Clustering analysis was used to identify patterns of coffee drinking timing.

Proton Pump Inhibitor Use and Incident Cardiovascular Disease in Older Postmenopausal Women.

Background: Epidemiological studies have been inconsistent regarding an association between proton pump inhibitor (PPI) use and risk of primary cardiovascular disease (CVD) events.

Methods: We studied 85,189 postmenopausal women (mean age 63 years at baseline) without known CVD at enrollment into the Women's Health Initiative Observational Study (1993-1998). PPI use was determined from medication inventories at baseline and Year-3.

Associations of blood pressure with white matter hyperintensities later in life; influence of short-term menopausal hormone therapy.

Objective: To assess the association of systolic and diastolic blood pressure (SBP and DBP) in recently menopausal women with white matter hyperintensity (WMH) volume later in life and determine whether short-term menopausal hormone therapy (mHT) modifies these associations.

Methods: Kronos Early Estrogen Prevention Study (KEEPS) was a multicenter, randomized, double-blinded, placebo-controlled 4-year mHT trial (oral conjugated equine estrogens or transdermal 17β-estradiol). KEEPS continuation was an observational follow-up of the participants 10 years after the end of mHT.

Epigenome-wide Association Analysis of Mitochondrial Heteroplasmy Provides Insight into Molecular Mechanisms of Disease.

The relationship between mitochondrial DNA (mtDNA) heteroplasmy and nuclear DNA (nDNA) methylation (CpGs) remains to be studied. We conducted an epigenome-wide association analysis of heteroplasmy burden scores across 10,986 participants (mean age 77, 63% women, and 54% non-White races/ethnicities) from seven population-based observational cohorts. We identified 412 CpGs (FDR p < 0.

The effect of vitamin D supplementation on the incidence of type 2 diabetes in healthy older adults not at high risk for diabetes (FIND): a randomised controlled trial.

Aims/hypothesis: Vitamin D insufficiency is associated with an elevated risk of type 2 diabetes, but evidence from randomised trials on the benefits of vitamin D supplementation is limited, especially for average-risk populations. The Finnish Vitamin D Trial (FIND) investigated the effects of vitamin D supplementation at two different doses on the incidence of type 2 diabetes in a generally healthy older adult population.

Methods: FIND was a 5 year randomised placebo-controlled, parallel-arm trial among 2271 male and female participants aged ≥60 years and ≥65 years, respectively, from a general Finnish population who were free of CVD or cancer and did not use diabetes medications.

Long-term cognitive effects of menopausal hormone therapy: Findings from the KEEPS Continuation Study.

Background: Findings from Kronos Early Estrogen Prevention Study (KEEPS)-Cog trial suggested no cognitive benefit or harm after 48 months of menopausal hormone therapy (mHT) initiated within 3 years of final menstrual period. To clarify the long-term effects of mHT initiated in early postmenopause, the observational KEEPS Continuation Study reevaluated cognition, mood, and neuroimaging effects in participants enrolled in the KEEPS-Cog and its parent study the KEEPS approximately 10 years after trial completion. We hypothesized that women randomized to transdermal estradiol (tE2) during early postmenopause would show cognitive benefits, while oral conjugated equine estrogens (oCEE) would show no effect, compared to placebo over the 10 years following randomization in the KEEPS trial.

Modifiable lifestyle factors in the primordial prevention of hypertension in three US cohorts.

Background: Evidence is lacking on the relative contributions of specific lifestyle factors and their overall contribution to prevention of hypertension, in particular early-onset hypertension.

Methods: This prospective cohort study included participants of the Nurses' Health Study (NHS, N = 52,780 women, aged 40-67 in 1986), the NHS II (N = 83,871 women, aged 27-46 in 1991), and the Health Professionals Follow-up Study (HPFS, N = 31,269 men, aged 40-75 in 1986), who were free from hypertension, cardiovascular disease and cancer at baseline. Four modifiable lifestyles were evaluated based on hypertension guidelines: BMI, moderate-to-vigorous physical activity, Dietary Approaches to Stop Hypertension (DASH) score, and alcohol intake.

Biomarkers of glucose-insulin homeostasis and incident type 2 diabetes and cardiovascular disease: results from the Vitamin D and Omega-3 trial.

Background: Dysglycemia and insulin resistance increase type 2 diabetes (T2D) and cardiovascular disease (CVD) risk, yet associations with specific glucose-insulin homeostatic biomarkers have been inconsistent. Vitamin D and marine omega-3 fatty acids (n-3 FA) may improve insulin resistance. We sought to examine the association between baseline levels of insulin, C-peptide, HbA1c, and a novel insulin resistance score (IRS) with incident cardiometabolic diseases, and whether randomized vitamin D or n-3 FA modify these associations.

Life's Essential 8 and Incident Cardiovascular Disease in U.S. Women With Breast Cancer.

Background: Relationships between lifestyle risk factors and cardiovascular disease (CVD) risk in women with breast cancer (BC) are underexplored.

Objectives: To evaluate the incidence of CVD in relation to the Life's Essential 8 (LE8) score among women with BC.

Methods: Data from the Women's Health Initiative were utilized.

Effects of healthy low-carbohydrate diet and time-restricted eating on weight and gut microbiome in adults with overweight or obesity: Feeding RCT.

The effect of a healthy low-carbohydrate diet (HLCD) and time-restricted eating (TRE), alone or in combination, on body weight and gut microbiome beyond caloric restriction remains unclear. In this 12-week two-by-two factorial randomized trial with a 28-week follow-up among 96 participants with overweight or obesity, isocaloric-restricted feeding yields significant weight loss, ranging from 2.57 to 4.

Associations between birthweight and preterm birth and the ages at menarche and menopause.

Background: Women who reach menarche and menopause at earlier ages have been shown to be at increased risk for numerous conditions including cardiovascular disease, cancer, depression, and obesity; however, risk factors for earlier ages of menarche and menopause are not fully understood. Therefore, we aimed to perform a retrospective investigation of the associations between a personal birthweight and/or being born preterm and the age of and menarche and menopause and related events in the Women's Health Initiative, a large, racially and ethnically diverse cohort of postmenopausal women.

Methods: At study entry, women reported their birthweight by category (< 6 lbs.

Proteomic signatures of healthy dietary patterns are associated with lower risks of major chronic diseases and mortality.

Healthy dietary patterns have been linked to a decreased risk of chronic diseases. However, it remains uncertain whether proteomic signatures can reflect proteome response to healthy diet patterns, and whether these proteomic signatures are associated with health outcomes. Using data from the UK Biobank including Olink plasma proteins, we identified substantial proteomic variation in relation to adherence to eight healthy dietary patterns.

Potato Consumption and Risk of Type 2 Diabetes Mellitus: A Harmonized Analysis of 7 Prospective Cohorts.

Background: Data on the relation of potato consumption with risk of type 2 diabetes (T2D) are limited and inconsistent. It is unclear whether the plant-based diet index (PDI), which is a novel and comprehensive tool to assess overall dietary pattern, modifies the association of potato intake with T2D.

Objectives: We examined the association of total, combined baked, boiled, and mashed potatoes and fried potatoes with risk of T2D and test the interaction between PDI score and potato consumption on T2D risk.

Circulating dimethylguanidino valeric acid, dietary factors, and risk of coronary heart disease.

Aims: Circulating dimethylguanidino valeric acid (DMGV) was identified as a novel metabolite related to cardiorespiratory fitness and cardiometabolic abnormalities. Circulating DMGV levels are subjective to dietary modulation; however, studies on its associations with intakes of coronary heart disease (CHD)-related foods/nutrients are limited. We investigated whether plasma DMGV was related to risk of incident CHD.