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To determine the association of weight loss and the onset of dementia of the Alzheimer type (DAT) and to characterize the rate of weight change over time in older adults (aged 65-95 years) who develop DAT vs those who remain without dementia.Design: Rates of weight change were investigated in older adult research participants (N = 449) who were enrolled as control subjects without dementia and followed up longitudinally (6 years on average) at the Alzheimer's Disease Research Center, Washington University School of Medicine. Some individuals (n = 125) eventually developed DAT; the others (n = 324) remained without dementia. Body weight was measured at each annual assessment. Piecewise linear regression and random effects models were used to test longitudinal rates of weight change between the groups.Results: Participants without dementia lost about 0.6 lb per year. For those individuals who developed DAT, about 1 year before the detection of DAT, the rate of weight loss doubled (1.2 lb per year). As a group, participants who eventually developed DAT weighed less (about 8 pounds) at study enrollment (ie, when they did not have dementia) than participants who remained without dementia.Conclusions: Aging with and without DAT is associated with weight loss; however, weight loss may accelerate before the diagnosis of DAT. Specific factors contributing to weight loss are unknown, but these data suggest they operate before the development of DAT. Hence, weight loss may be a preclinical indicator of Alzheimer disease.

These findings support the hypothesis that the strategic location of white matter hyperintensities may be critical in late-life depression. Further, the correlation of neuropsychological deficits with the volumes of whole brain white matter hyperintensities and gray and white matter in depressed subjects but not comparison subjects supports the hypothesis of an interaction between these structural brain components and depressed status.

Context Research on “vascular depression” has used two approaches to subtype late life depression (LLD) based on executive dysfunction or white matter hyperintensity (WMH) severity. Objective Evaluate the relationship of neuropsychological performance and WMH to clinical response in LLD. Design 2-site prospective nonrandomized controlled trial. Setting Outpatient clinics at Washington University and Duke University. Participants 217 subjects age ≥ 60 met DSM-IV criteria for major depression, scored ≥ 20 (MADRS), received vascular risk factor (VRF) scores, neuropsychological testing and MRI scan; were excluded for cognitive impairment or severe medical disorders. Fazekas rating was conducted to grade WMH lesions. Intervention 12 weeks of sertraline treatment, titrated by clinical response. Outcome Montgomery-Asberg Depression Rating Scale (MADRS) score over time. Results Baseline neuropsychological factor scores correlated negatively with baseline Fazekas scores. A mixed model examined effects of predictor variables on MADRS scores over time. Baseline episodic memory (p = 0.002); language (p = 0.007); working memory (p = 0.01); processing speed (p = 0.0001); executive function factor scores (p = 0.002), and categorical Fazekas ratings (p = 0.049) predicted MADRS scores, controlling for age, education, age of onset and race. Controlling for baseline MADRS scores these factors remained significant predictors of decrease in MADRS scores except working memory and Fazekas ratings. 33% of subjects achieved remission (MADRS ≤ 7). Remitters differed from non-remitters in baseline cognitive processing speed, executive function, language, episodic memory and VRF scores. Discussion Comprehensive neuropsychological function and WMH severity predicted MADRS scores prospectively over a 12 week SSRI treatment course in LLD. Baseline neuropsychological function differentiated remitters from non-remitters and predicted time to remission in a proportional hazards model. Predictor variables correlated highly with VRF severity. These data support the vascular depression hypothesis and highlight the importance of linking subtypes based on neuropsychological function and white matter integrity.

Engaging underrepresented groups in outcomes research is a public health priority for reducing health and health care disparities; yet, engaging these groups is challenging. Failure to involve these underrepresented populations in research further exacerbates these disparities. This article presents the health and research priorities of diverse groups of underrepresented populations in biomedical research, their concerns for participating in research, and strategies to engage them in their healthcare and research studies. Eleven community listening sessions, ranging from 7 to 13 community members each (N = 117), representing racial/ethnic minority, economically disadvantaged (e.g., uninsured), and hearing impaired communities. We used an inductive, qualitative content analysis approach to analyze the data for emerging themes. We identified the following themes: Uncertainties of underrepresented populations regarding research participation; Ineffective communication about research opportunities and research findings; Research on primary care and prevention are priorities for underrepresented populations in research; and Research teams need training in cultural competence and humility. Underrepresented groups provided research priorities, concerns, and strategies to engage them in their healthcare and in research studies. Findings from this study could facilitate improvement of research participation among underrepresented groups, ultimately reducing health disparities and improving quality of life among groups commonly omitted from research recruitment and participation.

The All of Us Research Program (All of Us) is a national effort to accelerate health research by exploring the relationship between lifestyle, environment, and genetics. It is set to become one of the largest research efforts in U.S. history, aiming to build a national resource of data from at least one million participants. All of Us aims to address the need for more diversity in research and set the stage for that diversity to be leveraged in precision medicine research to come. This paper describes how the program assessed demographic characteristics of participants who have enrolled in other U.S. biomedical research cohorts to better understand which groups are traditionally represented or underrepresented in biomedical research. We 1) reviewed the enrollment characteristics of national cohort studies like All of Us, and 2) surveyed the literature, focusing on key diversity categories essential to the program's enrollment aims. Based on these efforts, All of Us emphasizes enrollment of racial and ethnic minorities, and has formally designated the following additional groups as historically underrepresented: individuals-with inadequate access to medical care; under the age of 18 or over 65; with an annual household income at or below 200% of the federal poverty level; who have a cognitive or physical disability; have less than a high school education or equivalent; are intersex; identify as a sexual or gender minority; or live in rural or non-metropolitan areas. Research accounting for wider demographic variability is critical. Only by ensuring diversity and by addressing the very barriers that limit it, can we position All of Us to better understand and tackle health disparities.

IMPORTANCE Awake prone positioning may improve hypoxemia among patients with COVID-19, but whether it is associated with improved clinical outcomes remains unknown.OBJECTIVE To determine whether the recommendation of awake prone positioning is associated with improved outcomes among patients with COVID-19-related hypoxemia who have not received mechanical ventilation.

ProblemEngaging communities in research increases its relevance and may speed the translation of discoveries into improved health outcomes. Many researchers lack training to effectively engage stakeholders, whereas academic institutions lack infrastructure to support community engagement.ApproachIn 2009, the Meharry-Vanderbilt Community-Engaged Research Core began testing new approaches for community engagement, which led to the development of the Community Engagement Studio (CE Studio). This structured program facilitates project-specific input from community and patient stakeholders to enhance research design, implementation, and dissemination. Developers used a team approach to recruit and train stakeholders, prepare researchers to engage with stakeholders, and facilitate an in-person meeting with both.OutcomesThe research core has implemented 28 CE Studios that engaged 152 community stakeholders. Participating researchers, representing a broad range of faculty ranks and disciplines, reported that input from stakeholders was valuable and that the CE Studio helped determine project feasibility and enhanced research design and implementation. Stakeholders found the CE Studio to be an acceptable method of engagement and reported a better understanding of research in general. A tool kit was developed to replicate this model and to disseminate this approach.Next StepsThe research core will collect data to better understand the impact of CE Studios on research proposal submissions, funding, research outcomes, patient and stakeholder engagement in projects, and dissemination of results. They will also collect data to determine whether CE Studios increase patient-centered approaches in research and whether stakeholders who participate have more trust and willingness to participate in research.