Cardiovascular Health, Race, and Decline in Cognitive Function in Midlife Women: The Study of Women's Health Across the Nation.

BACKGROUND: Cognitive decline may progress for decades before dementia onset. Better cardiovascular health (CVH) has been related to less cognitive decline, but it is unclear whether this begins early, for all racial subgroups, and all domains of cognitive function. The purpose of this study was to determine the impact of CVH on decline in the 2 domains of cognition that decline first in White and Black women at midlife. METHODS AND RESULTS: Subjects were 363 Black and 402 White women, similar in baseline age (mean±SD, 46.6±3.0 years) and education (15.7±2.0 years), from the Chicago site of the Study of Women's Health Across the Nation. Cognition, measured as processing speed and working memory, was assessed annually or biennially over a maximum of 20 years (mean±SD, 9.8±6.7 years). CVH was measured as Life's Essential 8 (blood pressure, body mass index, glucose, non-high-density lipoprotein cholesterol, smoking, physical activity, diet, sleep). Hierarchical linear mixed models identified predictors of cognitive decline with progressive levels of adjustment. There was a decline in processing speed that was explained by race, age, and the 3-way interaction of race, CVH, and time (F1,4308=8.8, P=0.003). CVH was unrelated to decline in White women but in Black women poorer CVH was associated with greater decline. Working memory did not decline in the total cohort, by race, or by CVH. CONCLUSIONS: In midlife Black women, CVH promotion may be a target for preventing the beginnings of cognitive decline, thereby enhancing independent living with aging.

Does the Cognitive Change Index Predict Future Cognitive and Clinical Decline? Longitudinal Analysis in a Demographically Diverse Cohort.

Background: The Cognitive Change Index (CCI) is a widely-used measure of self-perceived cognitive ability and change. Unfortunately, it is unclear if the CCI predicts future cognitive and clinical decline. Objective: We evaluated baseline CCI to predict transition from normal cognition to cognitive impairment in nondemented older adults and in predementia groups including, subjective cognitive decline, motoric cognitive risk syndrome, and mild cognitive impairment. Different versions of the CCI were assessed to uncover any differential risk sensitivity. We also examined the effect of ethnicity/race on CCI. Methods: Einstein Aging Study participants (N = 322, Mage = 77.57±4.96, % female=67.1, Meducation = 15.06±3.54, % non-Hispanic white = 46.3) completed an expanded 40-item CCI version (CCI-40) and neuropsychological evaluation (including Clinical Dementia Rating Scale [CDR], Montreal Cognitive Assessment, and Craft Story) at baseline and annual follow-up (Mfollow - up=3.4 years). CCI-40 includes the original 20 items (CCI-20) and the first 12 memory items (CCI-12). Linear mixed effects models (LME) and generalized LME assessed the association of CCI total scores at baseline with rate of decline in neuropsychological tests and CDR. Results: In the overall sample and across predementia groups, the CCI was associated with rate of change in log odds on CDR, with higher CCI at baseline predicting faster increase in the odds of being impaired on CDR. The predictive validity of the CCI broadly held across versions (CCI-12, 20, 40) and ethnic/racial groups (non-Hispanic black and white). Conclusions: Self-perception of cognitive change on the CCI is a useful marker of dementia risk in demographically/clinically diverse nondemented samples. All CCI versions successfully predicted decline.

Trajectories of Sleep Over Midlife and Incident Cardiovascular Disease Events in the Study of Women's Health Across the Nation.

BACKGROUND: Up to 50% of women report sleep problems in midlife, and cardiovascular disease (CVD) is the leading cause of death in women. How chronic poor sleep exposure over decades of midlife is related to CVD risk in women is poorly understood. We tested whether trajectories of insomnia symptoms or sleep duration over midlife were related to subsequent CVD events among SWAN (Study of Women's Health Across the Nation) participants, whose sleep was assessed up to 16 times over 22 years. METHODS: At baseline, SWAN participants (n=2964) were 42 to 52 years of age, premenopausal or early perimenopausal, not using hormone therapy, and free of CVD. They completed up to 16 visits, including questionnaires assessing insomnia symptoms (trouble falling asleep, waking up several times a night, or waking earlier than planned ≥3 times/week classified as insomnia), typical daily sleep duration, vasomotor symptoms, and depressive symptoms; anthropometric measurements; phlebotomy; and CVD event ascertainment (ie, fatal or nonfatal myocardial infarction, stroke, heart failure, revascularization). Sleep trajectories (ie, insomnia, sleep duration) were determined by means of group-based trajectory modeling. Sleep trajectories were tested in relation to CVD in Cox proportional hazards models (multivariable models: site, age, race and ethnicity, education, CVD risk factors averaged over visits; additional covariates: vasomotor symptoms, snoring, depression). RESULTS: Four trajectories of insomnia symptoms emerged: low insomnia symptoms (n=1142 [39% of women]), moderate insomnia symptoms decreasing over time (n=564 [19%]), low insomnia symptoms increasing over time (n=590 [20%]), and high insomnia symptoms that persisted (n=668 [23%]). Women with persistently high insomnia symptoms had higher CVD risk (hazard ratio, 1.71 [95% CI, 1.19, 2.46], P=0.004, versus low insomnia; multivariable). Three trajectories of sleep duration emerged: persistently short (~5 hours: n=363 [14%]), moderate (~6 hours: n=1394 [55%]), and moderate to long (~8 hours: n=760 [30%]). Women with persistent short sleep had marginally higher CVD risk (hazard ratio, 1.51 [95% CI, 0.98, 2.33], P=0.06, versus moderate; multivariable). Women who had both persistent high insomnia and short sleep had significantly elevated CVD risk (hazard ratio, 1.75 [95% CI, 1.03, 2.98], P=0.04, versus low insomnia and moderate or moderate to long sleep duration; multivariable). Relations of insomnia to CVD persisted when adjusting for vasomotor symptoms, snoring, or depression. CONCLUSIONS: Insomnia symptoms, when persistent over midlife or occurring with short sleep, are associated with higher CVD risk among women.

Menopausal vasomotor symptoms and plasma Alzheimer disease biomarkers.

BACKGROUND: Identifying risk factors for Alzheimer disease in women is important as women compose two-thirds of individuals with Alzheimer disease. Previous work links vasomotor symptoms, the cardinal menopausal symptom, with poor memory performance and alterations in brain structure, function, and connectivity. These associations are evident when vasomotor symptoms are monitored objectively with ambulatory skin conductance monitors. OBJECTIVE: This study aimed to determine whether vasomotor symptoms are associated with Alzheimer disease biomarkers. STUDY DESIGN: Between 2017 and 2020, the MsBrain study enrolled 274 community-dwelling women aged 45 to 67 years who had a uterus and at least 1 ovary and were late perimenopausal or postmenopausal status. The key exclusion criteria included neurologic disorder, surgical menopause, and recent use of hormonal or nonhormonal vasomotor symptom treatment. Women underwent 24 hours of ambulatory skin conductance monitoring to assess vasomotor symptoms. Plasma concentrations of Alzheimer disease biomarkers, including amyloid ß 42-to-amyloid ß 40 ratio, phosphorylated tau (181 and 231), glial fibrillary acidic protein, and neurofilament light, were measured using a single-molecule array (Simoa) technology. Associations between vasomotor symptoms and Alzheimer disease biomarkers were assessed via linear regression models adjusted for age, race and ethnicity, education, body mass index, and apolipoprotein E4 status. Additional models adjusted for estradiol and sleep. RESULTS: A total of 248 (mean age, 59.06 years; 81% White; 99% postmenopausal status) of enrolled MsBrain participants contributed data. Objectively assessed vasomotor symptoms occurring during sleep were associated with significantly lower amyloid ß 42/amyloid ß 40, (beta, -.0010 [standard error, .0004]; P=.018; multivariable), suggestive of greater brain amyloid ß pathology. The findings remained significant after additional adjustments for estradiol and sleep. CONCLUSION: Nighttime vasomotor symptoms may be a marker of women at risk of Alzheimer disease. It is yet unknown if these associations are causal.

Use of Antihypertensives, Blood Pressure, and Estimated Risk of Dementia in Late Life: An Individual Participant Data Meta-Analysis.

Importance: The utility of antihypertensives and ideal blood pressure (BP) for dementia prevention in late life remains unclear and highly contested. Objectives: To assess the associations of hypertension history, antihypertensive use, and baseline measured BP in late life (age >60 years) with dementia and the moderating factors of age, sex, and racial group. Data Source and Study Selection: Longitudinal, population-based studies of aging participating in the Cohort Studies of Memory in an International Consortium (COSMIC) group were included. Participants were individuals without dementia at baseline aged 60 to 110 years and were based in 15 different countries (US, Brazil, Australia, China, Korea, Singapore, Central African Republic, Republic of Congo, Nigeria, Germany, Spain, Italy, France, Sweden, and Greece). Data Extraction and Synthesis: Participants were grouped in 3 categories based on previous diagnosis of hypertension and baseline antihypertensive use: healthy controls, treated hypertension, and untreated hypertension. Baseline systolic BP (SBP) and diastolic BP (DBP) were treated as continuous variables. Reporting followed the Preferred Reporting Items for Systematic Review and Meta-Analyses of Individual Participant Data reporting guidelines. Main Outcomes and Measures: The key outcome was all-cause dementia. Mixed-effects Cox proportional hazards models were used to assess the associations between the exposures and the key outcome variable. The association between dementia and baseline BP was modeled using nonlinear natural splines. The main analysis was a partially adjusted Cox proportional hazards model controlling for age, age squared, sex, education, racial group, and a random effect for study. Sensitivity analyses included a fully adjusted analysis, a restricted analysis of those individuals with more than 5 years of follow-up data, and models examining the moderating factors of age, sex, and racial group. Results: The analysis included 17 studies with 34 519 community dwelling older adults (20 160 [58.4%] female) with a mean (SD) age of 72.5 (7.5) years and a mean (SD) follow-up of 4.3 (4.3) years. In the main, partially adjusted analysis including 14 studies, individuals with untreated hypertension had a 42% increased risk of dementia compared with healthy controls (hazard ratio [HR], 1.42; 95% CI 1.15-1.76; P = .001) and 26% increased risk compared with individuals with treated hypertension (HR, 1.26; 95% CI, 1.03-1.53; P = .02). Individuals with treated hypertension had no significant increased dementia risk compared with healthy controls (HR, 1.13; 95% CI, 0.99-1.28; P = .07). The association of antihypertensive use or hypertension status with dementia did not vary with baseline BP. There was no significant association of baseline SBP or DBP with dementia risk in any of the analyses. There were no significant interactions with age, sex, or racial group for any of the analyses. Conclusions and Relevance: This individual patient data meta-analysis of longitudinal cohort studies found that antihypertensive use was associated with decreased dementia risk compared with individuals with untreated hypertension through all ages in late life. Individuals with treated hypertension had no increased risk of dementia compared with healthy controls.

The quantity and quality of cardiovascular fat at mid-life and future cognitive performance among women: The SWAN cardiovascular fat ancillary study.

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 (ß[standard error (SE)] = 0.08 [0.04], P = 0.033), while higher thoracic PVAT radiodensity with lower future episodic (ß[SE] = -0.06 [0.03], P = 0.045) and working (ß[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.

Availability of healthy foods, fruit and vegetable consumption, and cognition among urban older adults.

BACKGROUND: . Although prior studies have examined the associations between neighborhood characteristics and cognitive health, little is known about whether local food environments, which are critical for individuals' daily living, are associated with late-life cognition. Further, little is known about how local environments may shape individuals' health-related behaviors and impact cognitive health. The aim of this study is to examine whether objective and subjective measures of healthy food availability are associated with ambulatory cognitive performance and whether behavioral and cardiovascular factors mediate these associations among urban older adults. METHODS: . The sample consisted of systematically recruited, community-dwelling older adults (N = 315, mean age = 77.5, range = 70-91) from the Einstein Aging Study. Objective availability of healthy foods was defined as density of healthy food stores. Subjective availability of healthy foods and fruit/vegetable consumption were assessed using self-reported questionnaires. Cognitive performance was assessed using smartphone-administered cognitive tasks that measured processing speed, short-term memory binding, and spatial working memory performance 6 times a day for 14 days. RESULTS: . Results from multilevel models showed that subjective availability of healthy foods, but not objective food environments, was associated with better processing speed (estimate= -0.176, p = .003) and more accurate memory binding performance (estimate = 0.042, p = .012). Further, 14~16% of the effects of subjective availability of healthy foods on cognition were mediated through fruit and vegetable consumption. CONCLUSIONS: . Local food environments seem to be important for individuals' dietary behavior and cognitive health. Specifically, subjective measures of food environments may better reflect individuals' experiences regarding their local food environments not captured by objective measures. Future policy and intervention strategies will need to include both objective and subjective food environment measures in identifying impactful target for intervention and evaluating effectiveness of policy changes.

Six multidimensional sleep health facets in older adults identified with factor analysis of actigraphy: Results from the Einstein Aging Study.

OBJECTIVES: The concept of multi-dimensional sleep health, originally based on self-report, was recently extended to actigraphy in older adults, yielding five components, but without a hypothesized rhythmicity factor. The current study extends prior work using a sample of older adults with a longer period of actigraphy follow-up, which may facilitate observation of the rhythmicity factor. METHODS: Wrist actigraphy measures of participants (N = 289, Mage = 77.2 years, 67% females; 47% White, 40% Black, 13% Hispanic/Others) over 2 weeks were used in exploratory factor analysis to determine factor structures, followed by confirmatory factor analysis on a different subsample. The utility of this approach was demonstrated by associations with global cognitive performance (Montreal Cognitive Assessment). RESULTS: Exploratory factor analysis identified six factors: Regularity: standard deviations of four sleep measures: midpoint, sleep onset time, night total sleep time (TST), and 24-hour TST; Alertness/Sleepiness (daytime): amplitude, napping (mins and #/day); Timing: sleep onset, midpoint, wake-time (of nighttime sleep); up-mesor, acrophase, down-mesor; Efficiency: sleep maintenance efficiency, wake after sleep onset; Duration: night rest interval(s), night TST, 24-hour rest interval(s), 24-hour TST; Rhythmicity (pattern across days): mesor, alpha, and minimum. Greater sleep efficiency was associated with better Montreal Cognitive Assessment performance (ß [95% confidence interval] = 0.63 [0.19, 1.08]). CONCLUSIONS: Actigraphic records over 2 weeks revealed that Rhythmicity may be an independent factor in sleep health. Facets of sleep health can facilitate dimension reduction, be considered predictors of health outcomes, and be potential targets for sleep interventions.

Carotid intima media thickness and white matter hyperintensity volume among midlife women.

INTRODUCTION: Carotid atherosclerosis may be associated with brain white matter hyperintensities (WMH). Few studies consider women at midlife, a critical time for women's cardiovascular and brain health. We tested the hypothesis that higher carotid intima media thickness (IMT) would be associated with greater WMH volume (WMHV) among midlife women. We explored interactions by apolipoprotein E (APOE) ε4 status. METHODS: Two hundred thirty-nine women aged 45 to 67 underwent carotid artery ultrasound, phlebotomy, and magnetic resonance imaging (MRI). One hundred seventy participants had undergone an ultrasound 5 years earlier. RESULTS: Higher IMT was associated with greater whole brain (B[standard error (SE)] = 0.77 [.31], P = 0.01; multivariable) and periventricular (B[SE] = 0.80 [.30], P = 0.008; multivariable) WMHV. Associations were observed for IMT assessed contemporaneously with the MRI and 5 years prior to the MRI. Associations were strongest for APOE ε4-positive women. DISCUSSION: Among midlife women, higher IMT was associated with greater WMHV. Vascular risk is critical to midlife brain health, particularly for APOE ε4-positive women.

Dose-response relationship between late-life physical activity and incident dementia: A pooled analysis of 10 cohort studies of memory in an international consortium.

INTRODUCTION: Though consistent evidence suggests that physical activity may delay dementia onset, the duration and amount of activity required remains unclear. METHODS: We harmonized longitudinal data of 11,988 participants from 10 cohorts in eight countries to examine the dose-response relationship between late-life physical activity and incident dementia among older adults. RESULTS: Using no physical activity as a reference, dementia risk decreased with duration of physical activity up to 3.1 to 6.0 hours/week (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.67 to 1.15 for 0.1 to 3.0 hours/week; HR 0.68, 95% CI 0.52 to 0.89 for 3.1 to 6.0 hours/week), but plateaued with higher duration. For the amount of physical activity, a similar pattern of dose-response curve was observed, with an inflection point of 9.1 to 18.0 metabolic equivalent value (MET)-hours/week (HR 0.92, 95% CI 0.70 to 1.22 for 0.1 to 9.0 MET-hours/week; HR 0.70, 95% CI 0.53 to 0.93 for 9.1 to 18.0 MET-hours/week). DISCUSSION: This cross-national analysis suggests that performing 3.1 to 6.0 hours of physical activity and expending 9.1 to 18.0/MET-hours of energy per week may reduce dementia risk.

Menopausal Vasomotor Symptoms and White Matter Hyperintensities in Midlife Women.

BACKGROUND AND OBJECTIVES: The menopause transition is increasingly recognized as a time of importance for women's brain health. A growing body of work indicates that the classic menopausal symptom, vasomotor symptom (VMS), may be associated with poorer cardiovascular health. Other work links VMS to poorer cognition. We investigate whether VMS, when rigorously assessed using physiologic measures, are associated with greater white matter hyperintensity volume (WMHV) among midlife women. We consider a range of potential explanatory factors in these associations and explore whether VMS are associated with the spatial distribution of WMHV. METHODS: Women aged 45-67 years and free of hormone therapy underwent 24 hours of physiologic VMS monitoring (sternal skin conductance), actigraphy assessment of sleep, physical measures, phlebotomy, and 3 Tesla neuroimaging. Associations between VMS (24-hour, wake, and sleep VMS, with wake and sleep intervals defined by actigraphy) and whole brain WMHV were considered in linear regression models adjusted for age, race, education, smoking, body mass index, blood pressure, insulin resistance, and lipids. Secondary models considered WMHV in specific brain regions (deep, periventricular, frontal, temporal, parietal, and occipital) and additional covariates including sleep. RESULTS: The study sample included 226 women. Physiologically assessed VMS were associated with greater whole brain WMHV in multivariable models, with the strongest associations observed for sleep VMS (24-hour VMS, B[SE] = 0.095 [0.045], p = 0.032; Wake VMS, B[SE] = 0.078 [0.046], p = 0.089, Sleep VMS, B[SE] = 0.173 [0.060], p = 0.004). Associations were not accounted for by additional covariates including actigraphy-assessed sleep (wake after sleep onset). When considering the spatial distribution of WMHV, sleep VMS were associated with both deep WMHV, periventricular WMHV, and frontal lobe WMHV. DISCUSSION: VMS, particularly VMS occurring during sleep, were associated with greater WMHV. Identification of female-specific midlife markers of poor brain health later in life is critical to identify women who warrant early intervention and prevention. VMS have the potential to serve as female-specific midlife markers of brain health in women.

The independent associations of anti-Müllerian hormone and estradiol levels over the menopause transition with lipids/lipoproteins: The Study of Women's health Across the Nation.

BACKGROUND: The menopause transition (MT) is linked to adverse changes in lipids/lipoproteins. However, the related contributions of anti-Müllerian hormone (AMH) and estradiol (E2) are not clear. OBJECTIVE: To evaluate the independent associations of premenopausal AMH and E2 levels and their changes with lipids/lipoproteins levels [total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein B (apoB) and apolipoprotein A-1 (apoA-1)] over the MT. METHODS: SWAN participants who transitioned to menopause without exogenous hormone use, hysterectomy, or bilateral oophorectomy with data available on both exposure and outcomes when they were premenopausal until the 1st visit postmenopausal were studied. RESULTS: The study included 1,440 women (baseline-age:mean±SD=47.4±2.6) with data available from up to 9 visits (1997-2013). Lower premenopausal levels and greater declines in AMH were independently associated with greater TC and HDL-C, whereas lower premenopausal levels and greater declines in E2 were independently associated with greater TG and apo B and lower HDL-C. Greater declines in AMH were independently associated with greater apoA-1, and greater declines in E2 were independently associated with greater TC and LDL-C. CONCLUSIONS: AMH and E2 and their changes over the MT relate differently to lipids/lipoproteins profile in women during midlife. Lower premenopausal and/or greater declines in E2 over the MT were associated with an atherogenic lipid/lipoprotein profile. On the other hand, lower premenopausal AMH and/or greater declines in AMH over the MT were linked to higher apo A-1 and HDL-C; the later found previously to be related to a greater atherosclerotic risk after menopause.

Discrimination and Education Quality Moderate the Association of Sleep With Cognitive Function in Older Black Adults: Results From the Einstein Aging Study.

OBJECTIVES: Heterogeneity among Black adults' experiences of discrimination and education quality independently influence cognitive function and sleep, and may also influence the extent to which sleep is related to cognitive function. We investigated the effect of discrimination on the relationship between objective sleep characteristics and cognitive function in older Black adults with varying education quality. METHOD: Cross-sectional analyses include Black participants in the Einstein Aging Study (N = 104, mean age = 77.2 years, 21% males). Sleep measures were calculated from wrist actigraphy (15.4 ± 1.3 days). Mean ambulatory cognitive function (i.e., spatial working memory, processing speed/visual attention, and short-term memory binding) was assessed with validated smartphone-based cognitive tests (6 daily). A modified Williams Everyday Discrimination Scale measured discriminatory experiences. Linear regression, stratified by reading literacy (an indicator of education quality), was conducted to investigate whether discrimination moderated associations between sleep and ambulatory cognitive function for individuals with varying reading literacy levels. Models controlled for age, income, sleep-disordered breathing, and sex assigned at birth. RESULTS: Higher reading literacy was associated with better cognitive performance. For participants with both lower reading literacy and more discriminatory experiences, longer mean sleep time was associated with slower processing speed, and lower sleep quality was associated with worse working memory. Later sleep midpoint and longer nighttime sleep were associated with worse spatial working memory for participants with low reading literacy, independent of their discriminatory experiences. DISCUSSION: Sociocultural factors (i.e., discrimination and education quality) can further explain the association between sleep and cognitive functioning and cognitive impairment risk among older Black adults.

Psychosocial impacts of the COVID-19 pandemic on women with trauma histories: Study of Women's Health Across the Nation (SWAN).

Older adults, particularly those with trauma histories, may be vulnerable to adverse psychosocial outcomes during the COVID-19 pandemic. We tested associations between prepandemic childhood abuse or intimate partner violence (IPV) and elevated depressive, anxiety, conflict, and sleep symptoms during the pandemic among aging women. Women (N = 582, age: 65-77 years) from three U.S. sites (Pittsburgh, Boston, Newark) of the longitudinal Study of Women's Health Across the Nation (SWAN) reported pandemic-related psychosocial impacts from June 2020-March 2021. Prepandemic childhood abuse; physical/emotional IPV; social functioning; physical comorbidities; and depressive, anxiety, and sleep symptoms were drawn from SWAN assessments between 2009 and 2017. There were no measures of prepandemic conflict. In total, 47.7% and 35.3% of women, respectively, reported childhood abuse or IPV. Using logistic regression models adjusted for age; race/ethnicity; education; site; prepandemic social functioning and physical comorbidities; and, in respective models, prepandemic depressive, anxiety, or sleep symptoms, childhood abuse predicted elevated anxiety symptoms, OR = 1.67, 95% CI [1.10, 2.54]; household conflict, OR = 2.19, 95% CI [1.32, 3.61]; and nonhousehold family conflict, OR = 2.14, 95% CI [1.29, 3.55]. IPV predicted elevated sleep problems, OR = 1.63, 95% CI [1.07, 2.46], and household conflict, OR = 1.96, 95% CI [1.20, 3.21]. No associations emerged for depressive symptoms after adjusting for prepandemic depression. Aging women with interpersonal trauma histories reported worse anxiety, sleep, and conflict during the COVID-19 pandemic than those without. Women's trauma histories and prepandemic symptoms are critical to understanding the psychosocial impacts of the pandemic.

Sleep timing, sleep regularity, and psychological health in early late life women: Findings from the Study of Women's Health Across the Nation (SWAN).

OBJECTIVES: To examine the associations of actigraphy-assessed sleep timing and regularity with psychological health in early late life women, whose circadian rhythms may be impacted by aging. DESIGN: Cross-sectional. PARTICIPANTS: A racially/ethnically diverse sample of 1197 community-dwelling women (mean age 65 years) enrolled in the Study of Women's Health Across the Nation. MEASURES: Actigraphy-assessed sleep measures included timing (mean midpoint from sleep onset to wake-up) and regularity (standard deviation of midpoint in hours). Psychological health measures included a composite well-being score, the Center for Epidemiological Studies Depression Scale, and the Generalized Anxiety Disorder-7 Scale. Linear and logistic regression models, adjusted for covariates (including sleep duration), tested associations between sleep and psychological health measures. RESULTS: After covariate adjustment, a sleep midpoint outside of 2:00-4: 00 AM was significantly associated with depressive symptoms (ß = 0.88, 95% CI = 0.06, 1.70) and scoring above the cut-point for clinically significant depressive symptoms (OR = 1.72, 95% CI = 1.15, 2.57). Sleep irregularity was significantly associated with lower psychological well-being (ß = -0.18, 95% CI = -0.33, -0.03), depressive (ß = 1.36, 95% CI = 0.29, 2.44) and anxiety (ß = 0.93, 95% CI = 0.40, 1.46) symptoms, and scoring above the cut-point for clinically significant depressive (OR = 1.68, 95% CI = 1.01, 2.79) and anxiety (OR = 1.62, 95% CI = 1.07, 2.43) symptoms. CONCLUSION: Above and beyond sleep duration, a sleep midpoint outside of 2:00-4:00 AM was associated with depressive symptoms while sleep irregularity was associated with multiple psychological health domains in late life women.

Menopause Is Associated with an Altered Gut Microbiome and Estrobolome, with Implications for Adverse Cardiometabolic Risk in the Hispanic Community Health Study/Study of Latinos.

Menopause is a pivotal period during which loss of ovarian hormones increases cardiometabolic risk and may also influence the gut microbiome. However, the menopause-microbiome relationship has not been examined in a large study, and its implications for cardiometabolic disease are unknown. In the Hispanic Community Health Study/Study of Latinos, a population with high burden of cardiometabolic risk factors, shotgun metagenomic sequencing was performed on stool from 2,300 participants (295 premenopausal women, 1,027 postmenopausal women, and 978 men), and serum metabolomics was available on a subset. Postmenopausal women trended toward lower gut microbiome diversity and altered overall composition compared to premenopausal women, while differing less from men, in models adjusted for age and other demographic/behavioral covariates. Differentially abundant taxa for post- versus premenopausal women included Bacteroides sp. strain Ga6A1, Prevotella marshii, and Sutterella wadsworthensis (enriched in postmenopause) and Escherichia coli-Shigella spp., Oscillibacter sp. strain KLE1745, Akkermansia muciniphila, Clostridium lactatifermentans, Parabacteroides johnsonii, and Veillonella seminalis (depleted in postmenopause); these taxa similarly differed between men and women. Postmenopausal women had higher abundance of the microbial sulfate transport system and decreased abundance of microbial ß-glucuronidase; these functions correlated with serum progestin metabolites, suggesting involvement of postmenopausal gut microbes in sex hormone retention. In postmenopausal women, menopause-related microbiome alterations were associated with adverse cardiometabolic profiles. In summary, in a large U.S. Hispanic/Latino population, menopause is associated with a gut microbiome more similar to that of men, perhaps related to the common condition of a low estrogen/progesterone state. Future work should examine similarity of results in other racial/ethnic groups. IMPORTANCE The menopausal transition, marked by declining ovarian hormones, is recognized as a pivotal period of cardiometabolic risk. Gut microbiota metabolically interact with sex hormones, but large population studies associating menopause with the gut microbiome are lacking. Our results from a large study of Hispanic/Latino women and men suggest that the postmenopausal gut microbiome in women is slightly more similar to the gut microbiome in men and that menopause depletes specific gut pathogens and decreases the hormone-related metabolic potential of the gut microbiome. At the same time, gut microbes may participate in sex hormone reactivation and retention in postmenopausal women. Menopause-related gut microbiome changes were associated with adverse cardiometabolic risk in postmenopausal women, indicating that the gut microbiome contributes to changes in cardiometabolic health during menopause.

Depressive symptoms mediate the relationship between diabetes and cognitive performance in a community-based sample of older adults.

AIMS: To evaluate whether diabetes and prediabetes are associated with impaired cognitive performance among older adults and examine depressive symptoms as a mediator. METHODS: We used cross-sectional data from the Einstein Aging Study, a systematically recruited, community-based cohort study of diverse older adults (N = 794; Age Mean (SD) = 78.9 (5.3); 64.4% Non-Hispanic White, 28.7% Non-Hispanic Black, 5.7% Hispanic). Diabetes status was established via self-reported diagnosis, prescribed medications, and fasting blood glucose. Depressive symptoms were assessed using the Geriatric Depression Scale. Cognitive tests included Digit Symbol, Trails-B, Free Recall, Category Fluency, Boston Naming, and Block Design. Linear regression and mediation analyses were applied. RESULTS: Compared to those without diabetes, diabetes was associated with worse performance on all cognitive tests (ps < 0.05), except Trails-B (p = 0.53), and increased depressive symptoms (p < 0.01). For diabetes, mediation via increased depressive symptoms was observed for Free Recall (p = 0.044), Category Fluency (p = 0.033), and Boston Naming (p = 0.048). CONCLUSIONS: Diabetes was consistently associated with worse cognitive performance and increased depressive symptoms among this older cohort, while prediabetes was not. Mediation findings suggest depressive symptoms may be a biobehavioral pathway linking diabetes and cognition, though the temporal sequence is unclear. If causal, addressing both diabetes and depressive symptoms among older adults may protect cognitive function.

Infertility, recurrent pregnancy loss, and risk of stroke: pooled analysis of individual patient data of 618 851 women.

OBJECTIVE: To examine the associations of infertility, recurrent miscarriage, and stillbirth with the risk of first non-fatal and fatal stroke, further stratified by stroke subtypes. DESIGN: Individual participant pooled analysis of eight prospective cohort studies. SETTING: Cohort studies across seven countries (Australia, China, Japan, Netherlands, Sweden, the United Kingdom, and the United States) participating in the InterLACE (International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events) consortium, which was established in June 2012. PARTICIPANTS: 618 851 women aged 32.0-73.0 years at baseline with data on infertility, miscarriage, or stillbirth, at least one outcome event (non-fatal or fatal stroke), and information on covariates were included; 93 119 women were excluded. Of the participants, 275 863 had data on non-fatal and fatal stroke, 54 716 only had data on non-fatal stroke, and 288 272 only had data on fatal stroke. MAIN OUTCOME AND MEASURES: Non-fatal strokes were identified through self-reported questionnaires, linked hospital data, or national patient registers. Fatal strokes were identified through death registry data. RESULTS: The median follow-up for non-fatal stroke and fatal stroke was 13.0 years (interquartile range 12.0-14.0) and 9.4 years (7.6-13.0), respectively. A first non-fatal stroke was experienced by 9265 (2.8%) women and 4003 (0.7%) experienced a fatal stroke. Hazard ratios for non-fatal or fatal stroke were stratified by hypertension and adjusted for race or ethnicity, body mass index, smoking status, education level, and study. Infertility was associated with an increased risk of non-fatal stroke (hazard ratio 1.14, 95% confidence interval 1.08 to 1.20). Recurrent miscarriage (at least three) was associated with higher risk of non-fatal and fatal stroke (1.35, 1.27 to 1.44, and 1.82, 1.58 to 2.10, respectively). Women with stillbirth were at 31% higher risk of non-fatal stroke (1.31, 1.10 to 1.57) and women with recurrent stillbirth were at 26% higher risk of fatal stroke (1.26, 1.15 to 1.39). The increased risk of stroke (non-fatal or fatal) associated with infertility or recurrent stillbirths was mainly driven by a single stroke subtype (non-fatal ischaemic stroke and fatal haemorrhagic stroke), while the increased risk of stroke (non-fatal or fatal) associated with recurrent miscarriages was driven by both subtypes. CONCLUSION: A history of recurrent miscarriages and death or loss of a baby before or during birth could be considered a female specific risk factor for stroke, with differences in risk according to stroke subtypes. These findings could contribute to improved monitoring and stroke prevention for women with such a history.

Pain in midlife women: a growing problem in need of further research.

More than 10% of American adults experience some level of daily pain, and nearly 40 million (17.6%) experience episodes of severe pain annually. Women are particularly impacted by both episodic and chronic pain with higher prevalence and a greater level of pain-related disability compared to men. Midlife is a critical period for women during which the frequency of pain complaints begins to increase. Although pain is known to be influenced and controlled by sex hormones, it has not been widely recognized as a symptom of the menopausal transition outside of the menopause research community. The recent thematic series in this journal has specifically highlighted pain related conditions including rheumatoid arthritis, migraine and abdominal pain for which the significance among midlife women is not typically recognized. The studies presented in this thematic series present a small fraction of relevant, understudied questions regarding pain and its impact on women in midlife. Addressing the gaps in knowledge will require longitudinal studies that consider the emergence of pain symptomatology in relation to midlife trajectories of other symptoms and health determinants, as well as further study of new and emerging therapies.

Education, Occupational Complexity, and Incident Dementia: A COSMIC Collaborative Cohort Study.

BACKGROUND: Education and occupational complexity are main sources of mental engagement during early life and adulthood respectively, but research findings are not conclusive regarding protective effects of these factors against late-life dementia. OBJECTIVE: This project aimed to examine the unique contributions of education and occupational complexity to incident dementia, and to assess the mediating effects of occupational complexity on the association between education and dementia across diverse cohorts. METHOD: We used data from 10,195 participants (median baseline age = 74.1, range = 58∼103), representing 9 international datasets from 6 countries over 4 continents. Using a coordinated analysis approach, the accelerated failure time model was applied to each dataset, followed by meta-analysis. In addition, causal mediation analyses were performed. RESULT: The meta-analytic results indicated that both education and occupational complexity were independently associated with increased dementia-free survival time, with 28%of the effect of education mediated by occupational complexity. There was evidence of threshold effects for education, with increased dementia-free survival time associated with 'high school completion' or 'above high school' compared to 'middle school completion or below'. CONCLUSION: Using datasets from a wide range of geographical regions, we found that both early life education and adulthood occupational complexity were independently predictive of dementia. Education and occupational experiences occur during early life and adulthood respectively, and dementia prevention efforts could thus be made at different stages of the life course.