Citations

Abstract Sex or gender differences in the risk of Alzheimer's disease and related dementias (ADRD) differ by world region, suggesting that there are potentially modifiable risk factors for intervention. However, few epidemiological or clinical ADRD studies examine sex differences; even fewer evaluate gender in the context of ADRD risk. The goals of this perspective are to: (1) provide definitions of gender, biologic sex, and sexual orientation. and the limitations of examining these as binary variables; (2) provide an overview of what is known with regard to sex and gender differences in the risk, prevention, and diagnosis of ADRD; and (3) discuss these sex and gender differences from a global, worldwide perspective. Identifying drivers of sex and gender differences in ADRD throughout the world is a first step in developing interventions unique to each geographical and sociocultural area to reduce these inequities and to ultimately reduce global ADRD risk. Highlights The burden of dementia is unevenly distributed geographically and by sex and gender. Scientific advances in genetics and biomarkers challenge beliefs that sex is binary. Discrimination against women and sex and gender minority (SGM) populations contributes to cognitive decline. Sociocultural factors lead to gender inequities in Alzheimer's disease and related dementias (ADRD) worldwide.

Ischemic stroke accounts for over 80% of all strokes and is one of the leading causes of mortality and permanent disability worldwide. Intravenous administration of recombinant tissue plasminogen activator (rt-PA) is an approved treatment strategy for acute ischemic stroke of large arteries within 4.5 h of onset, and mechanical thrombectomy can be used for large arteries occlusion up to 24 h after onset. Improving diagnostic work up for acute treatment, reducing onset-to-needle time and urgent radiological access angiographic CT images (angioCT) and Magnetic Resonance Imaging (MRI) are real problems for many healthcare systems, which limits the number of patients with good prognosis in real world compared to the results of randomized controlled trials. The applied endovascular procedures demonstrated high efficacy, but some cellular mechanisms, following reperfusion, are still unknown. Changes in the morphology and function of mitochondria associated with reperfusion and ischemia-reperfusion neuronal death are still understudied research fields. Moreover, future research is needed to elucidate the relationship between continuously refined imaging techniques and the variable structure or physical properties of the clot along with vascular permeability and the pleiotropism of ischemic reperfusion lesions in the penumbra, in order to define targeted preventive procedures promoting long-term health benefits.

Background: Some patients with heart failure (HF) will go on to develop advanced HF, characterized by severe HF symptoms despite attempts to optimize medical therapy. The goals of this study were to examine the risk of developing advanced HF in patients with newly diagnosed HF, identify risk factors for developing advanced HF, and evaluate the impact of advanced HF on outcomes. Methods: This was a population-based, retrospective cohort study of Olmsted County, Minnesota, residents with a new clinical diagnosis of HF between 2007 and 2017. Risk factors for the development of advanced HF (2018 European Society of Cardiology criteria) were examined using cause-specific Cox proportional hazard regression models. The associations of development of advanced HF with risks of hospitalization and mortality were examined using the Andersen-Gill and Cox models, respectively. Results: There were 4597 residents with incident HF from 2007 to 2017. The cumulative incidence of advanced HF was 11.5% (95% CI, 10.5%–12.5%) at 6 years after incident HF diagnosis overall and was 14.4% (95% CI, 12.3%–16.9%), 11.4% (95% CI, 8.9%–14.6%), and 11.7% (95% CI, 10.3%–13.2%) in patients with incident HF with reduced, mildly reduced, and preserved ejection fraction, respectively. Key demographics, comorbidities, and echocardiographic characteristics were independently associated with the development of advanced HF. Development of advanced HF was associated with increased risks of all-cause hospitalization (adjusted hazard ratio, 3.0 [95% CI, 2.7–3.4]; P <0.001), HF hospitalization (hazard ratio, 10.2 [95% CI, 8.7–12.1]), all-cause mortality (hazard ratio, 5.0 [95% CI, 4.5–5.6]; P <0.001), and cardiovascular mortality (hazard ratio, 7.8 [95% CI, 6.7–9.1]). Conclusions: In this population-based study, development of advanced HF was common and was associated with markedly increased morbidity and mortality.

AbstractObjectivesPersistent functional impairment is common in bipolar disorder (BD) and is influenced by a number of demographic, clinical, and cognitive features. The goal of this project was to estimate and compare the influence of key factors on community function in multiple cohorts of well‐characterized samples of individuals with BD.MethodsThirteen cohorts from 7 countries included n = 5882 individuals with BD across multiple sites. The statistical approach consisted of a systematic uniform application of analyses across sites. Each site performed a logistic regression analysis with empirically derived “higher versus lower function” as the dependent variable and selected clinical and demographic variables as predictors.ResultsWe found high rates of functional impairment, ranging from 41 to 75%. Lower community functioning was associated with depressive symptoms in 10 of 12 of the cohorts that included this variable in the analysis. Lower levels of education, a greater number of prior mood episodes, the presence of a comorbid substance use disorder, and a greater total number of psychotropic medications were also associated with low functioning.ConclusionsThe bipolar clinical research community is poised to work together to characterize the multi‐dimensional contributors to impairment and address the barriers that impede patients' complete recovery. We must also identify the core features which enable many to thrive and live successfully with BD. A large‐scale, worldwide, prospective longitudinal study focused squarely on BD and its heterogeneous presentations will serve as a platform for discovery and promote major advances toward optimizing outcomes for every individual with this illness.

BackgroundAdvanced diffusion‐based MRI biomarkers may provide insight into microstructural and perfusion changes associated with neurodegeneration and cognitive decline.PurposeTo assess longitudinal microstructural and perfusion changes using apparent diffusion coefficient (ADC) and intravoxel incoherent motion diffusion‐weighted imaging (IVIM‐DWI) parameters in cognitively impaired (CI) and healthy control (HC) groups.Study TypeProspective/longitudinal.PopulationTwelve CI patients (75% female) and 13 HC subjects (69% female).Field Strength/Sequence3 T; Spin‐Echo‐IVIM‐DWI.AssessmentTwo MRI scans were performed with a 12‐month interval. ADC and IVIM‐DWI metrics (diffusion coefficient [D] and perfusion fraction [f]) were generated from monoexponential and biexponential fits, respectively. Additionally, voxel‐based correlations were evaluated between change in Montreal Cognitive Assessment (ΔMoCA) and baseline imaging parameters.Statistical TestsAnalysis of covariance with sex and age as covariates was performed for main effects of group and time (false discovery rate [FDR] corrected) with post hoc comparisons using Bonferroni correction. Partial‐η2 and Hedges' g were used for effect‐size analysis. Spearman's correlations (FDR corrected) were used for the relationship between ΔMoCA score and imaging. P < 0.05 was considered statistically significant.ResultsSignificant differences were found for the main effects of group (HC vs. CI) and time. For group effects, higher ADC, IVIM‐D, and IVIM‐f were observed in the CI group compared to HC (ADC: 1.23 ± 0.08.10−3 vs. 1.09 ± 0.07.10−3 mm2/sec; IVIM‐D: 0.82 ± 0.01.10−3 vs. 0.73 ± 0.01.10−3 mm2/sec; and IVIM‐f: 0.317 ± 0.008 vs. 0.253 ± 0.009). Significantly higher ADC, IVIM‐D, and IVIM‐f values were observed in the CI group after 12 months (ADC: 1.45 ± 0.05.10−3 vs. 1.50 ± 0.07.10−3 mm2/sec; IVIM‐D: 0.87 ± 0.01.10−3 vs. 0.94 ± 0.02.10−3 mm2/sec; and IVIM‐f: 0.303 ± 0.007 vs. 0.332 ± 0.008), but not in the HC group at large effect size. ADC, IVIM‐D, and IVIM‐f negatively correlated with ΔMoCA score (ρ = −0.49, −0.51, and −0.50, respectively).Data ConclusionThese findings demonstrate that longitudinal differences between CI and HC cohorts can be measured using IVIM‐based metrics.Level of Evidence2Technical Efficacy Stage2

Background: An obesity paradox, with better long-term survival in obese patients undergoing percutaneous coronary intervention (PCI), has been well described. The association between obesity and health status outcomes after PCI is unknown. Methods: We prospectively enrolled 3,281 PCI patients in a 10-center observational cohort study and categorized their body mass index (BMI) into normal (18.5 to <25), overweight (25 to <30), obese (30 to <35) and morbidly obese (≥ 35).Generalized linear models were used to describe the association between BMI and health status measures at 6 & 12 months, after adjusting for baseline characteristics and health status scores. Health status outcomes included; Seattle Angina Questionnaire [SAQ] Angina Frequency (AF), and Quality of Life (QL) scores, as well as the EQ-5D visual analogue scale (EQ-5D VAS). Interaction with time was not significant, so an estimate of the average benefit over time was generated. Results: The distribution of patients’ BMI revealed that 17% were normal, 35% overweight, 28% obese and 20% morbidly obese. Compared with normal weight patients, morbidly obese individuals were younger (mean 60.8 yr vs. 67.9 yr) and had a higher prevalence of diabetes, hypertension and heart failure. They underwent radial artery access (12.0% vs. 7.0%) and drug eluting stent implantation (80.4% vs. 76.0%) more frequently. Unadjusted changes in scores were lower (worse) among morbidly obese as compared with normal weight patients for SAQ AF (mean difference [MD] -1.52; 95% Confidence Interval [CI] -3.05, -0.02), SAQ QL (MD -2.51; CI -4.48, -0.54), and EQ-5D VAS (MD -5.74;CI -7.52, -3.96). After adjustment, these differences were no longer significantly different for SAQ AF and SAQ QL (figure), although EQ-5D VAS scores remained lower among obese and morbidly obese patients. Conclusion: The overall health status was mildly worse among obese and morbidly obese individuals after PCI, but the benefits of PCI on patients’ disease-specific health status were similar across weight categories. This suggests that PCI is equally effective in improving angina and disease-specific quality of life, independent of patients’ weight.

Background: Obstructive sleep apnea (OSA) imposes an afterload burden on the left ventricle and increases the pressure gradient across the intrathoracic aorta. This might increase the likelihood of aortic dissection (AD). We hypothesized that patients with acute AD would have a high prevalence of previously undiagnosed OSA and a largely nocturnal presentation. Methods: 40 consecutive, consenting subjects with acute AD who survived to hospital discharge were collected from 4 institutions. Mean age was 57 (range 28-75), 24 were male. 25 had type A dissection and 15 type B. 37 completed the modified Berlin Questionnaire and 30 had attended overnight polysomnography. Presenting CT scans had aortic diameter measured at a) the sinotubular junction b) ascending aorta c) origin of innominate d) mid-arch e) origin of left subclavian f) mid-descending aorta g) level of diaphragm; CT scans at 3 months were available in 24 subjects. Results: AHI ranged from 0 - 89; prevalence of OSA (defined by apnea-hypopnea index [AHI] > 5) was 63%. There were no differences in aortic diameter at any level comparing OSA vs non-OSA, regardless of AHI cutoff (>5, >15, >30; figure). Over time aortic diameter decreased at the level of the sinotubular junction and ascending aorta (expected - due to surgery). Whether dissection occurred during overnight hours (10 PM - 7 AM) did not differ by presence/absence of OSA (regardless of AHI cutoff). In those with high-risk Berlin questionnaires (>=2 categories positive) 10/21 (48%) dissections occurred during sleeping hours vs 2/13 (15%) in low risk Berlin group (p = 0.08, Fisher’s exact test). Conclusions: Among patients with acute AD the prevalence of OSA was high. Aortic diameters, however, were not different according to level of AHI. Presence of OSA defined by polysomnography was not associated with a nocturnal presentation in this sample.

Introduction: Some patients with heart failure (HF) will go on to develop advanced HF, characterized by severe HF symptoms despite attempts to optimize medical therapy. Our understanding of advanced HF at a population level remains limited. The goals of this study were to determine the risk of developing advanced HF in patients with newly diagnosed HF, identify risk factors for developing advanced HF, and evaluate the impact of advanced HF on outcomes. Methods: This was a population-based, retrospective cohort study of Olmsted County, Minnesota residents with a new clinical diagnosis of HF between 2007-2017. The primary outcome was development of advanced HF, defined using the 2018 European Society of Cardiology Criteria. Risk factors for development of advanced HF from the time of incident HF diagnosis were examined using cause-specific Cox proportional hazard regression models. The associations of development of advanced HF with risks of hospitalization and mortality were examined using Andersen-Gill and Cox models, respectively, with advanced HF treated as a time dependent covariate. Results: There were 4597 residents with incident HF from 2007 to 2017. The cumulative incidence of advanced HF was 6.0%, 9.1%, and 11.5% at 2, 4, and 6 years after incident HF diagnosis. Characteristics independently associated with development of advanced HF included older age, male sex, diabetes, chronic obstructive pulmonary disease, peripheral vascular disease, lower serum sodium, worse right ventricular function, left atrial enlargement, higher estimated filling pressures, and higher right ventricular systolic pressure (p<0.05 for each). Development of advanced HF was associated with increased risks of all-cause hospitalization (adjusted HR 3.00; 95% CI 2.65-3.41, p<0.001), HF hospitalization (HR 10.24, 95% CI 8.67-12.10), all-cause mortality (HR 5.00, 95% CI 4.46-5.59, p<0.001), and cardiovascular mortality (HR 7.84, 95% CI 6.74-9.12). Conclusions: In this population-based study, clinical, laboratory and echocardiographic characteristics at the time of incident HF diagnosis were associated with future risk of advanced HF. Development of advanced HF was associated with markedly increased morbidity and mortality.