Introduction: Subjective cognitive decline (SCD) represents self-reported problems with memory, a possible early sign of dementia. Little is known about SCD among sexual and gender minority (SGM) adults who identify as lesbian, gay, bisexual, and/or transgender or gender non-binary. Methods: Data were weighted to represent population estimates from 25 states’ 2015–2018 Behavioral Risk Factor Surveillance System to describe SCD in adults ≥45 years by SGM status. Logistic regression tested associations between demographic and health conditions. Results: SCD prevalence was higher in SGM (15.7%; 95% confidence interval [CI]:13.1–18.2) than in non-SGM adults (10.5%; 95% CI:10.1–10.9; P <.0001). SGM adults with SCD were also more likely to report functional limitations due to SCD than non-SGM adults with SCD, 60.8% versus 47.8%, P =.0048. Differences in SCD by SGM status were attenuated after accounting for depression. Discussion: Higher prevalence of SCD in SGM adults highlights the importance of ensuring inclusive screenings, interventions, care services, and resources for SGM adults.

Neuroinflammation is associated with Alzheimer’s disease, but the application of cerebrospinal fluid measures of inflammatory proteins may be limited by overlapping pathways and relationships between them. In this work, we measure 15 cerebrospinal proteins related to microglial and T-cell functions, and show them to reproducibly form functionally-related groups within and across diagnostic categories in 382 participants from the Alzheimer’s Disease Neuro-imaging Initiative as well participants from two independent cohorts. We further show higher levels of proteins related to soluble tumor necrosis factor receptor 1 are associated with reduced risk of conversion to dementia in the multi-centered (p = 0.027) and independent (p = 0.038) cohorts of people with mild cognitive impairment due to predicted Alzheimer’s disease, while higher soluble TREM2 levels associated with slower decline in the dementia stage of Alzheimer’s disease. These inflammatory proteins thus provide prognostic information independent of established Alzheimer’s markers.

Background Black transgender women endure pervasive polyvictimization (experiencing multiple forms of violence throughout the lifespan). Polyvictimization is associated with poor mental health. Black transgender women also face barriers in access to healthcare, but the extent that such barriers modify the association between polyvictimization and poor mental health has not been described using convergent mixed-methods analysis. Methods This convergent mixed-methods secondary analysis employs an intersectional lens and integrates two inter-related datasets to describe barriers to healthcare and the extent that such barriers modify the association between polyvictimization and mental health among Black transgender women. Investigators used survey data (n = 151 participants) and qualitative interview data (n = 19 participants) collected from Black transgender women (age 18 years and older) in Baltimore, MD and Washington, DC between 2016 and 2018. Analyses include thematic content analysis, bivariate analysis, joint display, and multivariate linear regression analysis examining mediation and moderation. Results Joint display illuminated three domains to describe how barriers to healthcare present among Black transgender women–Affordability, Accessibility, and Rapport and Continuity. Independent t-tests revealed significantly higher polyvictimization, Post Traumatic Stress Disorder (PTSD), and depression scores among participants who reported at least one barrier to healthcare (BHI) compared to those who reported no barriers. BHI significantly moderated and partially mediated the association between polyvictimization and PTSD symptom severity and BHI fully mediated the association between polyvictimization and depressive symptom severity–when accounting for age and location. Discussion Findings highlight the importance of access to healthcare in modifying the association between polyvictimization and PTSD and depression symptom severity among Black transgender women. Findings call for immediate interventions aimed at reducing barriers to healthcare and improved training for clinical providers serving Black transgender women.

Menopausal hormone therapy (MHT) reportedly increases the risk of cognitive decline in women over age 65 y. It is unknown whether similar risks exist for recently postmenopausal women, and whether MHT affects mood in younger women. The ancillary Cognitive and Affective Study (KEEPS-Cog) of the Kronos Early Estrogen Prevention Study (KEEPS) examined the effects of up to 4 y of MHT on cognition and mood in recently postmenopausal women. KEEPS, a randomized, double-blinded, placebo-controlled clinical trial, was conducted at nine US academic centers. Of the 727 women enrolled in KEEPS, 693 (95.3%) participated in the ancillary KEEPS-Cog, with 220 women randomized to receive 4 y of 0.45 mg/d oral conjugated equine estrogens (o-CEE) plus 200 mg/d micronized progesterone (m-P) for the first 12 d of each month, 211 women randomized to receive 50 μg/d transdermal estradiol (t-E2) plus 200 mg/d m-P for the first 12 d of each month, and 262 women randomized to receive placebo pills and patches. Primary outcomes included the Modified Mini-Mental State examination; four cognitive factors: verbal learning/memory, auditory attention/working memory, visual attention/executive function, and speeded language/mental flexibility; and a mood measure, the Profile of Mood States (POMS). MHT effects were analyzed using linear mixed-effects (LME) models, which make full use of all available data from each participant, including those with missing data. Data from those with and without full data were compared to assess for potential biases resulting from missing observations. For statistically significant results, we calculated effect sizes (ESs) to evaluate the magnitude of changes. On average, participants were 52.6 y old, and 1.4 y past their last menstrual period. By month 48, 169 (24.4%) and 158 (22.8%) of the 693 women who consented for ancillary KEEPS-Cog were lost to follow-up for cognitive assessment (3MS and cognitive factors) and mood evaluations (POMS), respectively. However, because LME models make full use all available data, including data from women with missing data, 95.5% of participants were included in the final analysis (n = 662 in cognitive analyses, and n = 661 in mood analyses). To be included in analyses, women must have provided baseline data, and data from at least one post-baseline visit. The mean length of follow-up was 2.85 y (standard deviation [SD] = 0.49) for cognitive outcomes and 2.76 (SD = 0.57) for mood outcomes. No treatment-related benefits were found on cognitive outcomes. For mood, model estimates indicated that women treated with o-CEE showed improvements in depression and anxiety symptoms over the 48 mo of treatment, compared to women on placebo. The model estimate for the depression subscale was −5.36 × 10⁻²(95% CI, −8.27 × 10⁻²to −2.44 × 10^−2;ES = 0.49, p < 0.001) and for the anxiety subscale was −3.01 × 10⁻²(95% CI, −5.09 × 10⁻²to −9.34 × 10⁻³; ES = 0.26, p < 0.001). Mood outcomes for women randomized to t-E2 were similar to those for women on placebo. Importantly, the KEEPS-Cog results cannot be extrapolated to treatment longer than 4 y. The KEEPS-Cog findings suggest that for recently postmenopausal women, MHT did not alter cognition as hypothesized. However, beneficial mood effects with small to medium ESs were noted with 4 y of o-CEE, but not with 4 y of t-E2. The generalizability of these findings is limited to recently postmenopausal women with low cardiovascular risk profiles.

Research indicates that certain antihypertensive medications alter Alzheimer's disease (AD) biomarkers in Caucasians. The renin angiotensin system (RAS) regulates blood pressure (BP) in the body and the brain and may directly influence AD biomarkers, including amyloid-β (Aβ) neuropathology, cerebral blood flow (CBF), and inflammatory markers. This hypothesis is supported by studies, including ours, showing that antihypertensives targeting the RAS reduce the risk and slow the progression of AD in Caucasians. While mounting evidence supports a protective role of RAS medications in Caucasians, this mechanism has not been explored in African Americans. To assess the mechanism by which RAS medications modify the brain RAS, cerebrospinal fluid (CSF) Aβ, CBF, and inflammatory markers in African Americans, we are conducting an eight month, Phase Ib randomized, placebo controlled trial, enrolling 60 middle-aged (45-70 years), non-demented individuals, at risk for AD by virtue of a parental history. Participants include normotensive and treated hypertensives that have never been exposed to a RAS medication. Participants are randomized (1-:-1:1) by gender and BP medication use (yes/no) to one of three groups: placebo, or 20-mg, or 40-mg telmisartan (Micardis), to determine the dose required to penetrate the CNS. Our overarching hypothesis is that, compared to placebo, both doses of telmisartan will penetrate the CNS and produce salutary, dose dependent effects on the brain RAS as well as CSF Aβ, CBF, and CSF inflammatory markers in African Americans, over eight months. This manuscript describes the trial rationale and design.

Objective: The objective of the present study was to compare the efficacy of two forms of menopausal hormone therapy in alleviating vasomotor symptoms, insomnia, and irritability in early postmenopausal women during 4 years. Methods: A total of 727 women, aged 42 to 58, within 3 years of their final menstrual period, were randomized to receive oral conjugated estrogens (o-CEE) 0.45 mg (n = 230) or transdermal estradiol (t-E 2 ) 50 μg (n = 225; both with micronized progesterone 200 mg for 12 d each mo), or placebos (PBOs; n= 275). Menopausal symptoms were recorded at screening and at 6, 12, 24, 36, and 48 months postrandomization. Differences in proportions of women with symptoms at baseline and at each follow-up time point were compared by treatment arm using exact x 2 tests in an intent-to-treat analysis. Differences in treatment effect by race/ethnicity and body mass index were tested using generalized linear mixed effects modeling. Results: Moderate to severe hot flashes (from 44% at baseline to 28.3% for PBO, 7.4% for t-E 2 , and 4.2% for o-CEE) and night sweats (from 35% at baseline to 19% for PBO, 5.3% for t-E 2 , and 4.7% for o-CEE) were reduced significantly by 6 months in women randomized to either active hormone compared with PBO (P < 0.001 for both symptoms), with no significant differences between the active treatment arms. Insomnia and irritability decreased from baseline to 6 months postrandomization in all groups. There was an intermittent reduction in insomnia in both active treatment arms versus PBO, with o-CEE being more effective than PBO at 36 and 48 months (P =0.002 and 0.05) and t-E 2 being more effective than PBO at 48 months (P = 0.004). Neither hormone treatment significantly affected irritability compared with PBO. Symptom relief for active treatment versus PBO was not significantly modified by body mass index or race/ethnicity. Conclusions: Recently postmenopausal women had similar and substantial reductions in hot flashes and night sweats with lower-than-conventional doses of oral or transdermal estrogen. These reductions were sustained during 4 years. Insomnia was intermittently reduced compared with PBO for both hormone regimens.

Objective: This study determined whether two different formulations of hormone therapy (HT): oral conjugated equine estrogens (o-CEE; 0.45 mg/d, n = 209), transdermal 17β-estradiol (t-E2; 50 μg/d, n = 201) plus cyclic progesterone (Prometrium, 200 mg) or placebo (PBO, n = 243) affected sleep domains in participants of the Kronos Early Estrogen Prevention Study. Methods: Participants completed the Pittsburgh Sleep Quality Index at baseline and during the intervention at 6, 18, 36, and 48 months. Global sleep quality and individual sleep domain scores were compared between treatments using analysis of covariance, and correlated with vasomotor symptom (VMS) scores using Spearman correlation coefficients. Results: Global Pittsburgh Sleep Quality Index scores (mean 6.3; 24% with score > 8) were similar across groups at baseline and were reduced (improved sleep quality) by both HT (average change -1.27 [o-CEE] and -1.32 [t-E2] ) when compared with PBO (-0.60; P = 0.001 [o-CEE vs PBO] and P = 0.002 [t-E2 vs PBO] ). Domain scores for sleep satisfaction and latency improved with both HT. The domain score for sleep disturbances improved more with t-E2 than o-CEE or PBO. Global sleep scores significantly correlated with VMS severity (r s = 0.170, P < 0.001 for hot flashes; r s = 0.177, P < 0.001 for night sweats). Change in scores for all domains except sleep latency and sleep efficiency correlated with change in severity of VMS. Conclusions: Poor sleep quality is common in recently menopausal women. Sleep quality improved with both HT formulations. The relationship of VMS with domains of sleep suggests that assessing severity of symptoms and domains of sleep may help direct therapy to improve sleep for postmenopausal women.

Objectives: To examine the risk associated with the use of proton pump inhibitors (PPIs) of conversion to mild cognitive impairment (MCI), dementia, and specifically Alzheimer's disease (AD). Design: Observational, longitudinal study. Setting: Tertiary academic Alzheimer's Disease Centers funded by the National Institute on Aging. Participants: Research volunteers aged 50 and older with two to six annual visits; 884 were taking PPIs at every visit, 1,925 took PPIs intermittently, and 7,677 never reported taking PPIs. All had baseline normal cognition or MCI. Measurements: Multivariable Cox regression analyses evaluated the association between PPI use and annual conversion of baseline normal cognition to MCI or dementia or annual conversion of baseline MCI to dementia, controlling for demographic characteristics, vascular comorbidities, mood, and use of anticholinergics and histamine-2 receptor antagonists. Results: Continuous (always vs never) PPI use was associated with lower risk of decline in cognitive function (hazard ratio (HR) = 0.78, 95% confidence interval (CI) =0.66–0.93, P =.005) and lower risk of conversion to MCI or AD (HR = 0.82, 95% CI = 0.69–0.98, P =.03). Intermittent use was also associated with lower risk of decline in cognitive function (HR = 0.84, 95% CI = 0.76–0.93, P =.001) and risk of conversion to MCI or AD (HR = 0.82, 95% CI = 0.74–0.91, P =.001). This lower risk was found for persons with normal cognition or MCI. Conclusion: Proton pump inhibitors were not associated with greater risk of dementia or of AD, in contrast to recent reports. Study limitations include reliance on self-reported PPI use and lack of dispensing data. Prospective studies are needed to confirm these results to guide empirically based clinical treatment recommendations.

We read with interest Huang and colleagues’ description of early patients with 2019 novel coronavirus in China, their plasma inflammatory protein profiles, and the clinical and biochemical distinctions from SARS.1 We have routinely analyzed inflammatory protein levels in healthy aging, neurological disorders, and infectious diseases over 10 years,2–5 and we express the strongest caution in postulating therapeutic protocols based on uncontrolled plasma cytokine analysis. Plasma biomarkers (including those measured here) are gaining popularity due to ease of phlebotomy and availability of commercial assays, but their associations with disease are also notoriously difficult to reproduce across laboratories, cohorts, and assay platforms even in well-controlled settings.2 Reasons for this include non-standard protocols to generate plasma (from whole blood), unpublished half-lives for most proteins in blood (minutes to days), proprietary methods for quantitation (antigenic site for antibodies, peptide fragment for mass spectrometry), and absence of high quality reference values from well-characterized healthy subjects. Plasma cytokines independent of demographic factors are also highly correlated entities in health (Fig 1A, ​,B)B) as well as disease, and false associations can in turn result from effects of age or race (Fig 1C, ​,D).D). Thus, elevated Th2-related cytokines in 2019-nCoV better inform an intact Th1-Th2 axis than putative efficacy of immunomodulatory therapies.1 If blood cytokine profile (with or without immunophenotyping) are considered for biomarkers to complement drug development or clinical monitoring, we recommend with the greatest urgency the creation of an international reference laboratory to enhance rigor and translatability.

Background: Several studies have shown higher Alzheimer's disease (AD) incidence rates are in African-Americans (AAs) than Caucasians (CCs). If this finding is consistent across studies, it raises important etiologic questions regarding factors responsible for this discrepancy. It also affects the likely public health burden of AD in the US in the future, as the non-Caucasian population becomes the majority. Objective: Estimate the AA/CC rate ratio for AD incidence across all available studies. Methods: We conducted a meta-analysis of population-based studies for the rate ratio (RR) of AD incidence for AAs versus CCs, after identifying six relevant studies from the literature.We calculated an AA/CC rate ratio across all studies using inversevariance weighting, and assessed inter-study heterogeneity. Using these incidence data, as well as data on survival after diagnosis, and on all-cause mortality, we also estimated the US prevalence of AD among AAs and CCs. Results: There were six population-based studies with data comparing AD incidence between AAs and CCs, with an estimated 370 AA and 640 CC incident cases. The meta-analysis RR showed that the AD rate for AAs was 64% higher than for CCs (RR = 1.64 (95% CI 1.35-2.00)), with no evidence of heterogeneity.We estimated the current US AD prevalence for ages 65-90 to be 5.5% for CCs, and 8.6% for AAs (prevalence ratio 1.56). Conclusion: AAs have an increased risk of incident and prevalent AD compared to CCs for reasons which are unknown, but are hypothesized to reflect biological, psychological, and socioeconomic factors.