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Clinicians can encounter sex and gender disparities in diagnostic and therapeutic responses. These disparities are noted in epidemiology, pathophysiology, clinical manifestations, disease progression, and response to treatment. This Review discusses the fundamental influences of sex and gender as modifiers of the major causes of death and morbidity. We articulate how the genetic, epigenetic, and hormonal influences of biological sex influence physiology and disease, and how the social constructs of gender affect the behaviour of the community, clinicians, and patients in the health-care system and interact with pathobiology. We aim to guide clinicians and researchers to consider sex and gender in their approach to diagnosis, prevention, and treatment of diseases as a necessary and fundamental step towards precision medicine, which will benefit men's and women's health.

Evidence is reassuring for women needing a few years’ treatment for menopausal symptoms

Purpose of Review Sex differences in cognitive function are well documented yet few studies had adequate numbers of women and men living with HIV (WLWH; MLWH) to identify sex differences in neurocognitive impairment (NCI) and the factors contributing to NCI. Here, we review evidence that WLWH may be at greater risk for NCI. Recent Findings We conducted a systematic review of recent studies of NCI in WLWH versus MLWH. A power analysis showed that few HIV studies have sufficient power to address male/female differences in NCI but studies with adequate power find evidence of greater NCI in WLWH, particularly in the domains of memory, speed of information processing, and motor function. Summary Sex is an important determinant of NCI in HIV, and may relate to male/female differences in cognitive reserve, comorbidities (mental health and substance use disorders), and biological factors (e.g., inflammation, hormonal, genetic).

Those with mild cognitive impairment (MCI), a precursor to dementia, have a gut microbiome distinct from healthy individuals, but this has only been shown in healthy individuals, not in those exhibiting several risk factors for dementia. Using amplicon 16S rRNA gene sequencing in a case-control study of 60 older (ages 55–76), obese, predominately female, African American adults, those with MCI (cases) had different gut microbiota profiles than controls. While microbial community diversity was similar between cases and controls, the abundances of specific microbial taxa weren’t, such as Parabacteroides distasonis (lower in cases) and Dialister invisus (higher in cases). These differences disappeared after adjusting for markers of oxidative stress and systemic inflammation. Cognitive scores were positively correlated with levels of Akkermansia muciniphila , a bacterium associated with reduced inflammation. Our study shows that gut microbial composition may be associated with inflammation, oxidative stress, and MCI in those at high risk for dementia.

Abstract Study Objectives Sleep disturbance is common among midlife women. Poor self-reported sleep characteristics have been linked to cerebrovascular disease and dementia risk. However, little work has considered the relation of objectively assessed sleep characteristics and white matter hyperintensities (WMHs), a marker of small vessel disease in the brain. Among 122 midlife women, we tested whether women with short or disrupted sleep would have greater WMH, adjusting for cardiovascular disease (CVD) risk factors, estradiol, and physiologically assessed sleep hot flashes. Methods We recruited 122 women (mean age = 58 years) without a history of stroke or dementia who underwent 72 h of actigraphy to quantify sleep, 24 h of physiologic monitoring to quantify hot flashes; magnetic resonance imaging to assess WMH; phlebotomy, questionnaires, and physical measures (blood pressure, height, and weight). Associations between actigraphy-assessed sleep (wake after sleep onset and total sleep time) and WMH were tested in linear regression models. Covariates included demographics, CVD risk factors (blood pressure, lipids, and diabetes), estradiol, mood, and sleep hot flashes. Results Greater actigraphy-assessed waking after sleep onset was associated with more WMH [B(SE) = .008 (.002), p = 0.002], adjusting for demographics, CVD risk factors, and sleep hot flashes. Findings persisted adjusting for estradiol and mood. Neither total sleep time nor subjective sleep quality was related to WMH. Conclusions Greater actigraphy-assessed waking after sleep onset but not subjective sleep was related to greater brain WMH among midlife women. Poor sleep may be associated with brain small vessel disease at midlife, which can increase the risk for brain disorders.

Magnetic resonance imaging (MRI) at 7T has a superior signal‐to‐noise ratio to 3T but also presents higher signal inhomogeneities and geometric distortions. A key knowledge gap is to robustly investigate the sensitivity and accuracy of 3T and 7T MRI in assessing brain morphometrics. This study aims to (a) aggregate a large number of paired 3T and 7T scans to evaluate their differences in quantitative brain morphological assessment using a widely available brain segmentation tool, FreeSurfer, as well as to (b) examine the impact of normalization methods for subject variability and smaller sample sizes on data analysis. A total of 401 healthy participants aged 29–68 were imaged at both 3T and 7T. Structural T1‐weighted magnetization‐prepared rapid gradient‐echo (MPRAGE) images were processed and segmented using FreeSurfer. To account for head size variability, the brain volumes underwent intracranial volume (ICV) correction using the Residual (regression model) and Proportional (simple division to ICV) methods. The resulting volumes and thicknesses were correlated with age using Pearson's correlation and false discovery rate correction. The correlations were also calculated in increasing sample size from three to the whole sample to estimate the sample size required to detect aging‐related brain variation. Three hundred and fifty subjects (208 females) passed the image quality control, with 51 subjects excluded due to excessive motion artifacts on 3T, 7T, or both. 7T MRI showed an overall stronger correlation between morphometrics and age and a larger number of significantly correlated brain volumes and cortical thicknesses. While the ICV is consistent between both field strengths, the Residual normalization method shows markedly higher correlation with age for 3T when compared with the Proportional normalization method. The 7T results are consistent regardless of the normalization method used. In a large cohort of healthy participants with paired 3T and 7T scans, we compared the statistical performance in assessing age‐related brain morphological changes. Our study reaffirmed the inverse correlation between brain volumes and cortical thicknesses and age and highlighted varying correlations in different brain regions and normalization methods at 3T and 7T. 7T imaging significantly improves statistical power and thus reduces the required sample size. In this cohort of 350 participants with paired 3T and 7T scans, we compared the statistical performance in assessing age‐related brain morphological changes. For comparable statistical power at 3T, the required sample size for 7T is reduced for cortical and subcortical volumes and substantially reduced for cortical thickness.

Underserved women of color experience high rates of perinatal affective disorders, but most research to date on the natural history of these disorders has been conducted on White women. The present study investigated longitudinal changes in anxiety and depression in a sample of perinatal non-Hispanic Black and Latina women. Categorical (yes/no) measures of positive anxiety and depression screens, as well as total symptom scores, were measured longitudinally across the perinatal period in 178 women (115 non-Hispanic Black, 63 Latina) using the CAT-MH™, a computerized adaptive test. Time (up to 4 visits) and race/ethnicity effects were assessed in linear mixed effects models. Rates of positive anxiety screenings were 13.6%, 3.2%, 8.5%, and 0% in Latina women and 2.6%, 4.2%, 6.1%, and 5.8% in non-Hispanic Black women in the 1st, 2nd, and 3rd trimesters, and postpartum, respectively. Rates of positive anxiety screenings overall were highest in the first trimester (OR = 0.20; 95% CI 0.04–0.98), and there was a significant time-by-race/ethnicity interaction for positive anxiety screens (OR = 8.88; 95% CI 1.42–55.51), as positive screens were most frequent in the first trimester and sharply declined for Latina women, while rates were relatively consistent across the perinatal period in non-Hispanic Black women. Rates of positive depression screens did not change over time, but there was a trend (OR = 1.93; 95% CI 0.93–4.03) for a time-by-race/ethnicity interaction in a direction similar to that seen for anxiety. The odds of positive anxiety screens vary by race/ethnicity and trimester, suggesting that anxiety screening and anxiety interventions may be most resourcefully used in the first trimester for Latina women in particular.

INTRODUCTION Although reproductive hormones are implicated in cerebral small vessel disease in women, few studies consider measured hormones in relation to white matter hyperintensity volume (WMHV), a key indicator of cerebral small vessel disease. Even fewer studies consider estrone (E1), the primary postmenopausal estrogen, or follicle‐stimulating hormone (FSH), an indicator of ovarian age. We tested associations of estradiol (E2), E1, and FSH to WMHV among women. METHODS Two hundred twenty‐two women (mean age = 59) underwent hormone assays (E1, E2, FSH) and 3T brain magnetic resonance imaging. Associations of hormones to WMHV were tested with linear regression. RESULTS Higher E2 (B[standard error (SE)] = –0.17[0.06], P = 0.008) and E1 (B[SE] = –0.26[0.10], P = 0.007) were associated with lower whole‐brain WMHV, and higher FSH (B[SE] = 0.26[0.07], P = 0.0005) with greater WMHV (covariates age, race, education). When additionally controlling for cardiovascular disease risk factors, associations of E1 and FSH to WMHV remained. DISCUSSION Reproductive hormones, particularly E1 and FSH, are important to women's cerebrovascular health. Highlights Despite widespread belief that sex hormones are important to women's brain health, little work has considered how these hormones in women relate to white matter hyperintensities (WMH), a major indicator of cerebral small vessel disease. We considered relations of estradiol (E2), estrone (E1), and follicle‐stimulating hormone (FSH) to WMH in midlife women. Higher E2 and E1 were associated with lower whole‐brain WMH volume (WMHV), and higher FSH with higher whole‐brain WMHV. Associations of E1 and FSH, but not E2, to WMHV persisted with adjustment for cardiovascular disease risk factors. Findings underscore the importance of E2 and FSH to women's cerebrovascular health.

To investigate if accounting for a cup-to-disc ratio (CDR) genetic risk score (GRS) modified the association between large CDR and cognitive function among women. This was a retrospective study using data from the Women's Health Initiative. Patients with glaucoma or ocular hypertension were excluded. Large CDR was defined as ≥ 0.6 in either eye. Cognitive function was measured by the Modified Mini-Mental State Examination (3MSE). We used the combined effects from 13 single nucleotide polymorphisms (SNPs) to formulate the GRS for CDR. We used logistic regression to investigate associations between weighted GRS and large CDR, then a linear regression to assess the association between weighted GRS and 3MSE scores, and between weighted GRS, CDR, and 3MSE scores, adjusted for demographic and clinical characteristics. Final analyses included 1,196 White women with mean age of 69.60 ± 3.62 years and 7.27% with large CDR. Mean GRS in women with and without large CDR was 1.51 ± 0.31 vs. 1.41 ± 0.36, respectively (p = 0.004). The odds of large CDR for a one unit increase in GRS was 2.30 (95% CI: (1.22, 4.36), p = 0.011). Adding the CDR GRS in the model with CDR and 3MSE, women with large CDR still had statistically significantly lower 3MSE scores than those without large CDR, yielding a predicted mean difference in 3MSE scores of 0.84 (p = 0.007). Independent of the CDR GRS, women with large CDR had a lower cognitive function.