BACKGROUND:: There is increasing evidence that depressive symptoms are associated with increased risk of cognitive impairment and dementia in older adults. In current study, we aimed to investigate the effect of depressive symptoms on incident Alzheimer disease and all-cause dementia in a community sample of older adults. METHODS:: Participants were 1219 older adults from the Einstein Aging Study, a longitudinal cohort study of community-dwelling older adults in Bronx County, New York. The Geriatric Depression Scale (GDS, 15-item) was used as a measure of depressive symptoms. The primary outcome was incident dementia diagnosed using the Diagnostic and Statistical Manual, Fourth Edition, criteria. Cox proportional hazard models were used to estimate the risk of incident dementia as a function of GDS score for the whole population and also for 2 different time intervals, <3 years and ≥3 years after baseline assessment. RESULTS:: Among participants, 132 individuals developed dementia over an average 4.5 years (standard deviation [SD] = 3.5) of follow-up. Participants had an average age of 78.3 (SD = 5.4) at baseline, and 62% were women. Among all participants, after controlling for demographic variables and medical comorbidities, a 1-point increase in GDS was associated with higher incidence of dementia (hazard ratio [HR] = 1.11, P = .007). After up to 3 years of follow-up, depressive symptoms were not significantly associated with dementia incidence (HR = 1.09; P = .070). However, after more than 3 years, GDS score was a significant predictor of incident dementia (HR = 1.13, P = .028). CONCLUSIONS:: Our results suggest that depressive symptoms are associated with an increased risk of incident dementia in older adults.

Introduction

Cardiovascular risk factors in midlife have been linked to late life risk for Alzheimer's disease and related dementias (ADRD). The relation of vascular risk factors on cognitive decline within midlife has been less studied.

Methods

Using data from the Study of Women's Health Across the Nation, we examined associations of midlife hypertension, elevated lipid levels, diabetes, fasting glucose, central adiposity, and Framingham heart age with rates of cognitive decline in women who completed multiple cognitive assessments of processing speed, and working and verbal memory during midlife.

Results

Diabetes, elevated fasting glucose, central obesity, and heart age greater than chronological age were associated with rate of decline in processing speed during midlife. Vascular risk factors were not related to rate of decline in working or verbal memory.

Discussion

Midlife may be a critical period for intervening on cardiovascular risk factors to prevent or delay later life cognitive impairment and ADRD.

Objective

To better understand how to educate patients and providers about study findings relevant to treatment guidelines, we assessed pre- versus post-Women's Health Initiative (WHI) differences in menopausal hormone therapy (MHT) initiation and continuation and their correlates, and in women's reasons for initiation and discontinuation.

Methods

We analyzed survey data from up to 14 approximately annual visits over 17 years (1996-2013) from 3,018 participants in the Study of Women's Health Across the Nation, a prospective cohort study. We used logistic regression to compare pre- versus post-WHI associations of covariates with MHT initiation and continuation, and to compare pre- versus post-WHI reasons for initiation and continuation.

Results

MHT initiation dropped from 8.6% pre-WHI to 2.8% post-WHI (P < 0.0001), and the corresponding decrease in MHT continuation was 84.0% to 62.0% (P < 0.0001). Decreases in MHT initiation and continuation occurred across a range of participant subgroups, consistent with wide dissemination of post-WHI recommendations. However, contrary to current guidelines, we found large declines in MHT use in subgroups for whom MHT is often recommended, that is, younger women and those with more vasomotor symptoms. Post-WHI, women's reasons for MHT initiation and discontinuation reflected concerns highlighted by WHI results. The largest declines in initiation reasons were for reducing risks of osteoporosis and heart disease, whereas the largest increases in discontinuation reasons were for media reports and provider advice.

Conclusions

Immediate post-WHI recommendations for MHT use were widely adopted. MHT risks documented in older women, however, may have led younger symptomatic women to forgo MHT for symptom relief.

Background

Exposures to ambient gaseous pollutants have been linked to cardiovascular diseases (CVDs), but the biological mechanisms remain uncertain.

Objectives

This study examined the changes in CVD marker levels resulting from elevated exposure to ambient gaseous pollutants in midlife women.

Methods

Annual repeated measurements of several inflammatory, hemostatic and lipid makers were obtained from 2306 midlife women enrolled in the longitudinal Study of Women's Health Across the Nation (SWAN) between 1999 and 2004. Ambient carbon monoxide (CO), nitrogen dioxide (NO₂), and sulfur dioxide (SO₂) data were assigned to each woman based on proximity of the monitoring station to her residential address. Short- and long-term exposures were calculated, and their associations with markers were examined using linear mixed-effects regression models, adjusted for demographic, health and other factors.

Results

Short-term CO exposure was associated with increased fibrinogen, i.e., every interquartile increase of average prior one-week exposure to CO was associated with 1.3% (95% CI: 0.6%, 2.0%) increase in fibrinogen. Long-term exposures to NO₂ and SO₂ were associated with reduced high-density lipoproteins and apolipoprotein A1, e.g., 4.0% (1.7%, 6.3%) and 4.7% (2.8%, 6.6%) decrease per interquartile increment in prior one-year average NO₂ concentration, respectively. Fine particle (PM_2.5) exposure confounded associations between CO/NO₂ and inflammatory/hemostatic markers, while associations with lipoproteins were generally robust to PM_2.5 adjustment.

Conclusions

Exposures to these gas pollutants at current ambient levels may increase thrombotic potential and disrupt cholesterol metabolism, contributing to greater risk of CVDs in midlife women. Caution should be exercised in evaluating the confounding by PM_2.5 exposure.

Background

Exposure to particulate matter air pollution has been associated with cardiovascular disease (CVD) morbidity and mortality; however, most studies have focused on fine particulate matter (PM_2.5) exposure and CVD. Coarse particulate matter (PM_10-2.5) exposure has not been extensively studied, particularly for long-term exposure, and the biological mechanisms remain uncertain.

Methods

We examined the association between ambient concentrations of PM_10-2.5 and inflammatory and hemostatic makers that have been linked to CVD. Annual questionnaire and clinical data were obtained from 1694 women (≥ 55 years old in 1999) enrolled in the longitudinal Study of Women's Health Across the Nation (SWAN) at six study sites from 1999 to 2004. Residential locations and the USEPA air monitoring network measurements were used to assign exposure to one-year PM_10-2.5, as well as co-pollutants. Linear mixed-effects regression models were used to describe the association between PM_10-2.5 exposure and markers, including demographic, health and other covariates.

Results

Each interquartile (4 μg/m³) increase in one-year PM_10-2.5 exposure was associated with a 5.5% (95% confidence interval [CI]: 1.8, 9.4%) increase in levels of plasminogen activator inhibitor-1 (PAI-1) and 4.1% (95% CI: - 0.1, 8.6%) increase in high-sensitivity C-creative Protein (hs-CRP). Stratified analyses suggested that the association with PAI-1 was particularly strong in some subgroups, including women who were peri-menopausal, were less educated, had a body mass index lower than 25, and reported low alcohol consumption. The association between PM_10-2.5 and PAI-1 remained unchanged with adjustment for PM_2.5, ozone, nitrogen dioxide, and carbon monoxide.

Conclusions

Long-term PM_10-2.5 exposure may be associated with changes in coagulation independently from PM_2.5, and thus, contribute to CVD risk in midlife women.

Introduction

Cardiovascular fat is a novel risk factor that may link to dementia. Fat volume and radiodensity are measurements of fat quantity and quality, respectively. Importantly, high fat radiodensity could indicate healthy or adverse metabolic processes.

Methods

The associations of cardiovascular fat (including epicardial, paracardial, and thoracic perivascular adipose tissue [PVAT]) quantity and quality assessed at mean age of 51 with subsequent cognitive performance measured repeatedly over 16 years of follow-up were examined using mixed models among 531 women.

Results

Higher thoracic PVAT volume was associated with a higher future episodic memory (β[standard error (SE)] = 0.08 [0.04], P = 0.033), while higher thoracic PVAT radiodensity with lower future episodic (β[SE] = -0.06 [0.03], P = 0.045) and working (β[SE] = -0.24 [0.08], P = 0.003) memories. The latter association is prominent at higher volume of thoracic PVAT.

Discussion

Mid-life thoracic PVAT may have a distinct contribution to future cognition possibly due to its distinct adipose tissue type (brown fat) and anatomical proximity to the brain circulation.

Highlights

Higher mid-life thoracic perivascular adipose tissue (thoracic PVAT) volume is related to a better future episodic memory in women. Higher mid-life thoracic PVAT radiodensity is related to worse future working and episodic memories. Negative association of high thoracic PVAT radiodensity with working memory is prominent at higher thoracic PVAT volume. Mid-life thoracic PVAT is linked to future memory loss, an early sign of Alzheimer's disease. Mid-life women's epicardial and paracardial fat are not related to future cognition.

Fine particles (PM_2.5) are known to increase risks of cardiovascular diseases, but it is unclear how they affect plasma lipid levels. In this study, we examined the associations between PM_2.5 exposure and lipid/lipoprotein levels from 2289 midlife women enrolled in the longitudinal Study of Women's Health Across the Nation. The average exposure to PM_2.5 and gaseous co-pollutants during the prior one year, six months, 30 days, and one day were estimated for each woman based on U.S. Environmental Protection Agency ambient monitoring data. Blood samples were collected annually from 1999 to 2005 and analyzed for lipids/lipoproteins. Mixed-effect models were used to account for repeated measures for each woman, adjusted for demographic, health and behavior covariates. PM_2.5 exposures, especially the long-term exposure, were negatively associated with protective lipoproteins, and positively associated with atherogenic lipoproteins. For example, each 3 μg/m³ increase of one-year PM_2.5 exposure was associated with decreases of -0.7% (-1.4%, -0.1%) in high-density lipoprotein cholesterols and -0.6% (-1.1%, -0.1%) in apolipoprotein A1 (ApoA1), as well as increases of 3.8% (1.0%, 6.6%) in lipoprotein(a) and 1.4% (0.5%, 2.3%) in the ratio of apolipoprotein B (ApoB)/ApoA1. In stratified analysis, increased atherogenic lipoproteins were mainly observed in women without dyslipidemia, and both increased atherogenic lipoproteins and reduced protective lipoproteins were observed among women in perimenopause. In summary, PM_2.5 exposure was associated with adverse lipid level changes, and thus, may increase cardiovascular risks in midlife women.

Associations between temperature and cardiovascular (CVD) mortality have been reported, but the underlying biological mechanisms remain uncertain. We explored the association between apparent temperature and serum biomarkers for CVD. Using linear mixed effects models, we examined the relationships between residence-proximate apparent temperature (same day and 1, 7, and 30 days prior) and several inflammatory, hemostatic, and lipid biomarkers for midlife women from 1999 through 2004. Our study population consisted of 2,306 women with mean age of 51 years (± 3 years) enrolled in Study of Women's Health Across the Nation (SWAN) in Chicago, Illinois; Detroit, Michigan; Los Angeles and Oakland, California; Newark, New Jersey; and Pittsburgh, Pennsylvania. Mean daily apparent temperature was calculated using temperature and relative humidity data provided by the National Climatic Data Center and the US Environmental Protection Agency, while daily data for fine particles, ozone, carbon monoxide, and nitrogen dioxide from the US Environmental Protection Agency Air Quality Data Mart were considered as confounders. All analyses were stratified by warm and cold seasons. More significant (p < 0.10) negative associations were found during the warm season for various lag times, including hs-CRP, fibrinogen, tissue plasminogen activator antigen (tPA-ag), tissue plasminogen activator antigen (PAI-1), Factor VIIc, high-density lipoprotein (HDL), and total cholesterol. During the cold season, significant negative associations for fibrinogen and HDL, but significant positive associations for tPA-ag, PAI-1, and triglycerides were observed for various lag times. With the exception of ozone, pollutants did not confound these associations. Apparent temperature was associated with several serum biomarkers of CVD risk in midlife women, shedding light on potential mechanisms.

Objective

The menopausal transition is characterized by progressive changes in ovarian function and increasing circulating levels of gonadotropins, with some women having irregular menstrual cycles well before their final menstrual period. These observations indicate a progressive breakdown of the hypothalamic-pituitary-ovarian axis often associated with an increase in menopausal symptoms. Relationships between vasomotor symptoms (VMS) and depressed mood and sleep as well as a bidirectional association between VMS and depressed mood in mid-life women have been reported, but the endocrine foundations and hormone profiles associated with these symptoms have not been well described. Our objective was to determine the relationship between daily urinary hormone profiles and daily logs of affect and VMS during the early perimenopausal transition.

Study design

SWAN, the Study of Women's Health Across the Nation, is a large, mutli-ethnic, multisite cohort study of 3302 women aged 42-52 at baseline, designed to examine predictors of health and disease in women as they traversed the menopause. Inclusion criteria were: an intact uterus and at least one ovary present, at least one menstrual period in the previous three months, no use of sex steroid hormones in the previous three months, and not pregnant or lactating. A subset (n = 849) of women aged 43-53 years from all study sites in the first Daily Hormone Study collection were evaluated for this substudy.

Outcome measures

We measured daily VMS, and urinary hormones: follicle stimulating hormone (FSH), luteinizing hormone (LH), pregnanediol glucuronide (PdG) and estradiol (estrone conjugate, E1C).

Results

A variable pattern of LH and negative LH feedback were the hormone patterns most strongly associated with increased VMS. In contrast, no hormone pattern was significantly related to negative mood.

Conclusion

Fluctuations of LH associated with low progesterone production were associated with VMS but not negative mood, suggesting different endocrine patterns may be related to increased negative mood than to the occurrence of VMS.

Background

Studies have reported associations between long-term air pollution exposures and cardiovascular mortality. The biological mechanisms connecting them remain uncertain.

Methods

We examined associations of fine particles (PM2.5) and ozone with serum markers of cardiovascular disease risk in a cohort of midlife women. We obtained information from women enrolled at six sites in the multi-ethnic, longitudinal Study of Women's Health Across the Nation, including repeated measurements of high-sensitivity C-reactive protein, fibrinogen, tissue-type plasminogen activator antigen, plasminogen activator inhibitor type 1, and factor VIIc (factor VII coagulant activity). We obtained residence-proximate PM2.5 and ozone monitoring data for a maximum five annual visits, calculating prior year, 6-month, 1-month, and 1-day exposures and their relations to serum markers using longitudinal mixed models.

Results

For the 2,086 women studied from 1999 to 2004, PM2.5 exposures were associated with all blood markers except factor VIIc after adjusting for age, race/ethnicity, education, site, body mass index, smoking, and recent alcohol use. Adjusted associations were strongest for prior year exposures for high-sensitivity C-reactive protein (21% increase per 10 μg/m³ PM2.5, 95% confidence interval [CI]: 6.6, 37), tissue-type plasminogen activator antigen (8.6%, 95% CI: 1.8, 16), and plasminogen activator inhibitor (35%, 95% CI: 19, 53). An association was also observed between year prior ozone exposure and factor VIIc (5.7% increase per 10 ppb ozone, 95% CI: 2.9, 8.5).

Conclusions

Our findings suggest that prior year exposures to PM2.5 and ozone are associated with adverse effects on inflammatory and hemostatic pathways for cardiovascular outcomes in midlife women.