Claude D. Pepper Older Americans Independence Center

Raymond Yung, M.D.
Principal Investigator
Stephanie Gatica, B.A.
Program Administrator

Funded by the NIA as the nations first Geriatric Research and Training Center in 1989, the University of Michigan (UM) Pepper Center has evolved to meet the objectives of the OAIC program with successful competing renewals as an OAIC in 1994, 1999, 2004, 2009, 2015, and 2020. Thus, our Center is completing its 31st consecutive year of operation in 2020. The overarching goal of the UM Pepper Center is to create, enhance and maintain a cohesive intellectual, technological, and administrative environment to maximize geriatrics research that will promote health and functional independence in older adults. Drawing on the large base of research currently underway in the fields of geriatrics and gerontology at UM, the UM Pepper Center fosters collaborative multidisciplinary research to integrate basic science, clinical science, and health services research relevant to the health care problems of older adults. The UM Pepper Center grant supports important research activities of the UM Geriatrics Center. Founded in 1987, the Geriatrics Center is the umbrella organization for geriatrics research, education, and patient care at the University of Michigan. The specific goals of the UM Pepper Center are:To support research that will improve understanding of how metabolic factors and inflammation interact with age-related diseases and comorbidities to determine key health outcomes related to mobility and functional status.

  • To support translational research on the interaction of metabolic factors and inflammation with age-related diseases and comorbidities to improve health outcomes related to mobility and functional status.
  • To provide Resource Cores that support and assist investigator-initiated projects related to the UM Pepper Center’s research focus.
  • Through its Research Education Core (REC), to strengthen the UM environment for training of future academic leaders in geriatrics and aging who can conduct research related to the UM Pepper Center’s research focus.
  • Through its Pilot and Exploratory Studies Core (PESC), to attract UM junior faculty, as well as selected senior faculty not previously involved in aging research, to develop new research projects related to the UM Pepper Center’s research focus.

Faculty from the following UM Schools and Institutes are involved: the Institute of Gerontology, School of Public Health, Institute for Social Research, Medical School, College of Engineering, School of Nursing, School of Social Work, and College of Literature, Science, and the Arts. As of 2018 there were 89 active NIA grants at the UM with over $60 million/year of total costs. The UM OAIC’s faculty participant data base includes a total of 239 current UM faculty who have 221 current external grants relevant to the UM Pepper Center’s focus totaling over $57 million/year direct costs.

Leadership and Administrative Core (LAC)
Leader 1:    Raymond Yung, MD
Leader 2:    Lona Mody, MD, MSc
A well-defined and effective Leadership Administrative Core (LAC) that supports the rich activities of the OAIC is already in place. The faculty and staff in the LAC have proven leadership and administrative skills. The LAC will foster critical interactions among the OAIC Program Director, the OAIC Core Directors/Co-Directors and the leadership structure of the Institution as a whole. These linkages are fostered by the proven administrative structure, which requires meetings of the OAIC leadership on a regular and ongoing basis, and of key advisory committees: the UM Geriatrics Center’s Research Operating Committee (ROC) and the OAIC External Advisory Board (EAB). The ROC, led by two fellowship-trained geriatricians/physician scientists (Yung, Mody) with complementary expertise and research interests, provides strategic planning, coordination and oversight for all OAIC activities. The membership of the ROC includes the LAC Leader and Co-Leader, the former OAIC Director, the ten other OAIC Core Directors/Co-Directors, and Geriatrics Center administrative leaders.

Research Education Component (REC)
Leader 1:    Neil B. Alexander, MD
Leader 2:    Lillian Min, MD, MSHS
Leader 3:    Carrie Karvonen-Gutierrez
The REC is a component of the Claude D. Pepper Older Americans Independence Center, funded by the National Institute on Aging. The primary goal of the Research Education Core is to recruit, select, support, mentor, and train junior faculty to become independent investigators in aging-related research and academic leaders in geriatrics and gerontology within their respective disciplines. The REC focuses on stimulating the translation between basic and clinical research across the spectrum of its training activities, including the annual research education core retreat(link is external). To this end it serves a critical function in supporting the overall OAIC focus by training the next generation of investigators whose research will lead to an improved understanding of the predictors and modulators of the aging phenotype.

Pilot and Exploratory Studies Core (PESC)
Leader 1:    Lona Mody, MD
Leader 2:    Donovan Maust, MD
The goal of the Pilot and Exploratory Studies Core is to provide support for studies that will develop and test new research ideas of high relevance to the Center's overall theme: “To improve understanding of how metabolic factors and inflammation interact with age-related diseases and comorbidities to determine key health outcomes related to mobility and functional status” The PESC will thus fund pilot research studies over a wide range of disciplines, ranging from basic genetics and physiology through behavioral and health services research.

Leader 1:    James Ashton-Miller, PhD
Leader 2:    Neil Alexander, MD
The Biomechanics Core provides an array of techniques and equipment for the precise experimental quantification of physical functioning of healthy and frail elders in order to investigate attributes of the aging phenotype. It also supplies support for theoretical investigations in the form of computer simulation models to analyze the elements of those functional abilities and to establish the major determinants of abilities to perform motor acts in an effective manner. The Core is physically based in the Biomechanics Research Laboratory(link is external) (directed by Dr. Ashton-Miller) and the Mobility Research Center(link is external) (directed by Dr. Alexander). Physical disabilities are epidemic in the elderly. Whatever the underlying pathologies, these disabilities express themselves in biomechanical terms: reduced muscular strengths and rates of developing strengths, limited ranges and speeds of motion, reduced afferent feedback, inappropriate body segment coordination patterns, difficulty with balance and fall arrests, and even impaired pelvic floor and continence system function. The Biomechanics Core will contribute to the development of academic leaders in geriatrics by helping interested faculty and their fellows to analyze a range of geriatric problems through biomechanical research techniques. Thus, it will train them through directed study involving background reviews, hypothesis generation, interdisciplinary pilot research projects, and data analysis and interpretation to examine issues adversely affecting the physical abilities of the elderly.

Core Facility for Aged Rodents (CFAR)
Leader 1:    Richard Miller, MD, PhD
The Core Facility for Aged Rodents, CFAR, has been a major feature of the University of Michigan Claude Pepper Center since its inception in 1989. CFAR serves the needs of Pepper Center investigators through four Specific Aims. CFAR will provide advice to all OAIC investigators, from student through faculty levels, in the use of rodents for research into the biology of aging and its role in late life disease. CFAR will support specialized colonies of mice particularly well suited for research on the biology of aging and its relationship to late-life disease. These include (a) genetically heterogeneous mice of the UM-HET3 stock; (b) calorically restricted UM-HET3 mice; and (c) mice of the long-lived Snell dwarf (dw/dw) stock, carrying the Pit1 dw mutation. Mice from these colonies will be provided to faculty members working on Pilot Studies Exploratory Core (PESC) and Research Career Development Core (RCDC) research projects, as well as to Geriatrics Center faculty members who wish to conduct pilot studies on mouse aging supported by other sources of NIA funds. CFAR funds will support the development of new animal models for specific purposes. In the first year, these will include a new four-way cross suitable for studies of late-life hearing loss.

Design, Data, and Biostatistics Core (DDBC)
Leader 1:    Andrzej Galecki, PhD, MD
Leader 2:    Julie Bynum, M.D., M.Ph.
The Design, Data, and Biostatistics Core (DDBC) will provide technical support and training of investigators developing or performing intervention and other geriatric research projects examining the aging phenotype and outcomes research. It will also develop new instruments, methodologies, and data archives to enable future studies. Thus the DDBC will both address techniques for appropriate design and execution of current experiments and set the foundation for future research studies. Building on our experience with the UM Pepper Center, the DDBC will address the needs of OAIC investigators, and especially junior investigators, for assistance in the design of intervention experiments, and the collection, maintenance, analysis, and interpretation of their data.

Human Subjects and Assessment (HSAC)
Leader 1:    Raymond Yung, MD
Leader 2:    Kenneth Langa, MD, PhD
The Human Subjects and Assessment Core (HSAC) supports activities involving human subjects at the University of Michigan Claude D. Pepper Center. It has four specific aims: HSAC will establish, maintain, and facilitate access to human subjects and related data sets. HSAC will expand, promote and facilitate access to minority human subjects through collaborative linkages with the Wayne State University Institute of Gerontology (WSU IoG). HSAC aims to provide selected efficient physical health measures, which will complement our existing collection of self-reported health, health care utilization, and psychosocial measures in subject selection. HSAC will provide training and consultation to investigators on issues related to (a) recruitment and retention of human subjects, and (b) measurement of quality of life and psychosocial factors closely linked with aging phenotype.

REC Scholar, Research & Grants Funded During Pepper Supported Time Years /
Emily Briceno, Ph.D.
Clinical Assistant Professor / Department of Physical Medicine & Rehabilitation
Measurement of cognition across language and education among Mexican American and non-Hispanic white older adults
2021-2023 /
4 (total)
2 (1st/Sr)
Joseph Endicott, M.D.
Research Investigator / Department of Pathology
Metabolic reprogramming by chaperone-mediated autophagy downstream of the lifespan-extending PTEN transgene
2022-2023 /
3 (total)
3 (1st/Sr)
David Flood, M.D., M.Sc.
Clinical Instructor / Department of Internal Medicine
Cross-national comparisons of disability among older adults with diabetes in 23 countries
2022-2023 /
4 (total)
2 (1st/Sr)
Victoria Powell, M.D.
Clinical Instructor / Division of Geriatric and Palliative Medicine
Recruiting Older Adult Research Participants: Considerations, Sources, and Methods
2022-2023 /
31 (total)
17 (1st/Sr)
Michael Smith, PharmD
Clinical Associate Professor / Department of Pharmacy
Understanding medication use in older adult cancer survivors with centralized pain, focusing on practice patterns
2021-2022 /
9 (total)
5 (1st/Sr)
Matthew Pianko, M.D.
Clinical Assistant Professor / Department of Internal Medicine
Evaluating the impact of immunosenescence and inflammaging on vaccine-induced immunity in older adults with plasma cell neoplasms
2021-2022 /
4 (total)
3 (1st/Sr)

Past Scholars
Marco Cassone, MD, PhD, University of Michigan, Geriatrics & Palliative Medicine (2018-2020)
Jaclynn Hawkins, University of Michigan School of Social Work (2019-2020)
Xiaoling Xiang, University of Michigan School of Social Work (2019-2021)
Jiha Lee, MD, MHS, University of Michigan (2019-2021)

1. Project Title: Viral Infection Burden and Immunosenescence
  Leader: Grace Noppert, Ph.D.
  LAC Year 17 (7/1/21-6/30/22) *RAPID PILOT* Adults aged 65+ years account for 45% of hospitalizations and 53% of intensive care admissions due to COVID-19 despite comprising 17% of the U.S. population. The systemic hyperinflammatory response is a key feature observed in many severe cases of COVID-19 and may signal an underlying immunopathology related to substantial T cell stimulation. This immunopathology is likely an indication of advanced immunological age, or immunosenescence. irhe mechanisms underlying the increased risk for severe outcomes, including mortality, from COVID-19 among older adults are still being elucidated. Emerging evidence suggests that viral infections may accelerate the pace of immunosenescence. However, significant questions remain With regards to the role of viral co-infections, differential immune control of viral infections, and the ??pecific changes in the immune compartment induced by viral infections. Our long-term goal is to examine the role of viral infections in driving population-level patterns of immunosenescence. The overall obiective of the current application is to characterize the viral burden resulting from five herpesviruses by examining both seropositivity to each virus as well as antibody level with higher antibody levels reflecting worse immune control of the virus and thus a greater burden to the immune system. Using previously collected human samples from the University of Michigan's Central Biorepository, we will first characterize the viral infection burden to five human herpesesviruses and describe differences by age, race/ethnicity, and gender (Aim 1 ). We will then estimate whether viral infection burden is associated with advanced immunosenescence in the T cell compartment (Aim 2). At its conclusion, these pilot data will shed further light on the immune parameters most likely to be affected by viral infections. Ultimately, the goal of this work to provide insights into future development of interventions that can address long-term immune consequences older adults are likely to continue to face due to viral infections.
2. Project Title: Aging and tryptophan immune metabolism in CKD associated cardiovascular disease
  Leader: Anna Mathew, M.B.B.S.
  PESC Year 17 (7/1/21-6/30/22) Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in chronic kidney disease (CKD), reducing CKD patients' life expectancy. However, the accelerated CVD pathogenesis in CKD is not yet clearly understood, and no specific therapeutic strategies are currently available to attenuate this phenomenon. Our Jong-term goal is to understand the role of aging and immune-metabolic mechanisms underlying accelerated atherosclerosis to improve CKD patients' lifespan. Our overall objective is to define the role of aging and tryptophan catabolism via the kynurenine pathway (KP) in the pathophysiology of CKD atherosclerosis. Our central hypothesis is that the macrophage-derived tryptophan catabolite kynurenic acid (KA) causes CKD atherosclerosis in older CKD patients, whereas 3-hydroxy anthranilic acid (3-HAA) ameliorates this problem. Our rationale is that if KP metabolites play a causal role in CKD atherosclerosis in older adults, then we can develop new therapeutic strategies and biomarkers to attenuate the CVD burden in the CKD population. We will test our central hypothesis by pursuing the following specific aims: 1) demonstrating the role of aging and macrophage-derived KP metabolites in the pathophysiology of CKD related CVD, and 2) delineating the mechanisms downstream of KP metabolites (namely KA and 3-HM) in the pathogenesis of CKD atherosclerosis. Under Aim 1, we will delineate the role of aging and peripheral blood mononuclear cell KP metabolism on CVD in CKD patients. Regarding Aim 2, we plan to demonstrate that KA causes CKD atherosclerosis by acting on macrophage cytosolic aryl hydrocarbon and cell-membrane G protein-coupled receptor 35 receptors, whereas 3-HM ameliorates CKD atherosclerosis by acting on the macrophage inflammasome using primary macrophage cultures.
3. Project Title: Aging Associated Transcriptional Changes of Metabolic Pathways in the Kidney
  Leader: Jennifer Schaub, M.D.
  PESC Year 16 (7/1/20-6/30/21) Chronic Kidney Disease (CKD) is a global health epidemic, particularly among the elderly. Pathologic analysis of the aging kidney shows nephrosclerosis, which includes global glomerulosclerosis, interstitial fibrosis, tubular atrophy and atherosclerosis. Vascular changes are an integral part of nephrosclerosis and may be linked to tubular injury and atrophy, but this is understudied because it is difficult to assess the vasculature, which is often not sampled in kidney biopsy specimens. While interstitial fibrosis and tubular atrophy are the strongest known pathologic predictors of progression of CKD, we have limited understanding of how vascular disease and aging contributes to tubular cell atrophy and transcriptional changes in glycolysis and oxidative metabolism pathways. It is critical to better understand how transcriptional regulation of these metabolic pathways in tubular cells are altered with aging and vascular disease, as Prolyl Hydroxylase Inhibitors (PHI), novel therapeutic agents that increase the activity of Hypoxia Inducible Factors, are effective treatments for anemia of CKD. Mechanistic data shows that PHI may alter transcriptional regulation of metabolic pathways within the kidney and could alter the progression of kidney disease. The PRECISE cohort, a cohort of nephrectomy specimens, has abundant sampling of vasculature and is a unique opportunity to evaluate the relationship between aging, vascular disease, tubular atrophy and transcriptional regulation of metabolism. The proposed studies will assess a) the relationship between tubular atrophy, vascular disease and aging from a morphometric perspective and b) the changes in the tubular cell specific expression of genes involved in glycolysis and oxidative metabolism in those with vascular disease and aging kidneys. We will then generate the transcriptional data from kidneys that have already been harvested from the Glenn Mouse Aging Study and align these results with the human data. In addition, we will use publically available gene expression data from animal models treated with PHI to assess how these agents impact transcriptional expression of metabolic pathways. Results from these studies can be used for potential future collaborations with the Core Facility for Slow Aging Mice.
4. Project Title: Supporting older adults with cognitive impairment before elective surgery; Developing a measure of preoperative preparedness of patient-caregiver dyads
  Leader: Alexandra Norcott, M.D., M.Sc.
  PESC Year 17 (7/1/21-6/30/22) The proposed study has two specific aims: 1. Identify the core domains of transitional preparedness to address in the preoperative period: We will conduct pre and postoperative qualitative interviews of patients with cognitive impairment and their designated caregivers to identify core domains of transitional preparedness. We will also measure caregivers' perceived locus of control and caregiving contributions. 2.Develop a preoperative measure of dyad transitional preparedness: Using the HSAC volunteer pool, we will develop a measure of dyad transitional preparedness in older adults with cognitive impairment. We will then evaluate our measure's validity and reliability in 20 dyads before elective surgery. Significance: Data from this study will serve as pilot data for a successful application for a career development award where this tool can be validated in a larger population of caregivers; and, the association between d ad re aredness and ost-o erative outcomes can be tested.
5. Project Title: The Neural Mechanisms Linking Hearing Loss and Cognitive Decline in Aging
  Leader: Gideon Rothschild, Ph.D.
  PESC Year 17 (7/1/21-6/30/22) Mounting epidemiological studies in recent years suggest that hearing loss is associated with cognitive decline in both normal aging and dementia. However, whether these findings reflect a causal link, and if so- by what neural mechanisms, remains unknown. Determining whether hearing loss causally promotes cognitive decline and identifying the underlying neural mechanisms would have far-reaching clinical implications to benefit the aging population. To address this goal, here we propose to combine cutting edge electrophysiological recording techniques with neural inactivation in mice models of aging. We will focus on a critical yet understudied communication pathway between the auditory cortex (AC) and the lateral entorhinal cortex (LEC). This channel of communication links the auditory system with the hippocampal memory circuit, and is thus a major candidate pathway underlying the link between hearing loss and cognitive decline. While it is well-established that noise-induced hearing loss (NIHL) induces aberrant hyperactivity in the AC, the consequence on the LEC remains unknown. We will record neural activity across the AC and LEC in awake mice and examine how NIHL influences communication and neural information processing across these regions. We will then use chemogenetic neural inactivation to determine the causal influence of AC hyperactivity on the downstream LEC target. Finally, we will test the consequence of AC hyperactivity on behavioral memory performance. Together, our experiments will provide critical causal and mechanistic insight regarding the link between hearing loss and cognitive decline.
6. Project Title: Age-specific biomechanical model of pelvic floor support
  Leader: Luyun Chen, M.S., M.A., Ph.D.
  PESC Year 17 (7/1/21-6/30/22) The goal of this pilot study is to quantify the age-related ICM and cardinal ligament (CL) length change per decade in living women (Aim 1) and create an age-specific pelvic floor biomechanical model to investigate the aging's contribution to the POP development (Aim 2). Aim 1: Secondary MRI analysis for aging-related ICM shape change and its correlation with levator 'bowl‘ volume (LBV) and cardinal ligament (CL) length.: Develop MRI-based shape analysis strategy to quantify the age-related change on ICM among "young" (<40 y), "mid-age" (50-60 y) and "old" (;:=:70 y) nulliparous women. We expect that concaved ICM in "older" women contribute to the increase of levator "bowl" volume resulting longer CL length. Aim 2: Age-specific pelvic floor biomechanical model: Create age-specific biomechanical model to investigate the contribution of age-specific change to the POP development using shape analysis to parameterize age-related ICM shape changes together with CL length change. An array of FEM models Mtith various degree age-related ICM changes loaded with increasing intra-abdominal pressure. The apical tension will be calculated as outcome variable. We expect age-related changes would greatly increasing the apical tension and increase the risk of POP development.
7. Project Title: The impact of frailty and immunosenescence on SARS-CoV-2 vaccination outcomes in older adults with plasma cell disorders
  Leader: Matthew Pianko, M.D.
  PESC Year 16 (7/1/20-6/30/21) The global pandemic infectious disease COVID-19 caused by severe acute respiratory coronavirus 2 (SARS-CoV-2) has caused worldwide devastation, and a strikingly high mortality rate of 30-55% in multiple myeloma (MM) patients aged 65 years or more. While the advent of effective and safe vaccines against SARS-CoV-2 provides hope, both MM patients and elderly adults are known to have suboptimal antibody responses to vaccines and the effectiveness of these novel vaccines in this population is unknown because immunocompromised persons were excluded from the phase Ill trials of SARS-CoV-2 vaccines. The long-term goal of this project is to gain deeper insight into the impacts of frailty and age-related immune dysfunction on immune response to vaccination in aged adults with plasma cell disorders in order to optimize vaccination strategies for these patients. The central hypothesis is that frailty can predict suboptimal immune responses to SARS-CoV-2 vaccinations in patients with plasma cell neoplasms. The rationale for this project is that frailty is predictive of clinical outcomes in MM and the aged immune system affects vaccine responses in frail and non-frail persons. The central hypothesis will be tested by pursuing two Specific Aims: 1) To estimate the impact of frailty on immunogenicity of SARS-CoV-2 vaccines in older adults with plasma cell neoplasms in a prospective pilot-phase observational cohort study; and 2) Determine the impact of B cell immunosenescence on SARS-CoV-2 vaccination outcomes in older adults with plasma cell neoplasms. Under the first Aim, a validated geriatric assessment will be performed, SARS-CoV-2 Spike antibodies will be quantified at 4-6 weeks after vaccination, and rates of suboptimal immune responses will be compared in frail and non-frail individuals stratified by clinical factors. Under the second Aim, functional assessment of antibody-binding affinity will be evaluated using a pseudo-typed virus neutralization assay. The research proposed in this application is innovative because it seeks to evaluate the impact of frailty on the immunogenicity of a novel vaccine type in a population at great need of protection from morbidity and mortality from severe COVID19. The proposed research is significant because it is expected to provide justification and preliminary data to prospectively evaluate methods to improve vaccination outcomes for individuals at high risk of lethal infectious diseases. This work will provide key support for career development and will fund generation of preliminary data to obtain external fundino support.
8. Project Title: Cross-national comparisons of disability among older adults with diabetes in 23 countries
  Leader: David Flood, M.D., M.Sc.
  PESC Year 18 (7/1/22-6/30/23) Diabetes is one of the most critical worldwide health issues for older adults. Research largely from high-income countries has shown that diabetes is associated with an increased risk of disability among older adults. However, there is limited understanding of how prevalence of disability among older adults with diabetes may be similar or different across the world. The objective of this pilot project is to assess cross-national patterns of disability among older adults with diabetes by leveraging the Global Gateway to Aging, an NIA-funded platform of harmonized data from international cohorts aligned with the U.S. Health and Retirement Study. Aim 1 will augment the Gateway to Global Aging platform by developing a harmonized measure of diabetes status in 23 countries that incorporates both questionnaire and blood-based biomarker data. Aim 2 will assess cross-national patterns of disability among older adults using the augmented Gateway to Global Aging dataset developed in Aim 1. This proposal’s focus strongly aligns with the Pepper Center’s overarching mission and will take advantage of unique expertise at the University of Michigan through interaction with Dr. Kenneth Langa (Human Subjects and Assessment Core) and Dr. Andrzej Galecki (Design, Data, and Biostatistics Core). If funded, this project will assist Dr. Flood’s career goal of developing expertise to conduct independent aging research.
9. Project Title: Metabolic reprogramming by chaperone-mediated autophagy downstream of the lifespan-extending PTEN transgene
  Leader: Joseph Endicott, Ph.D.
  PESC Year 18 (7/1/22-6/30/23) Maintaining the balance between glycolysis and oxidative phosphorylation is essential for disease-free aging. Oxidative capacity declines with age across diverse animal models, and compensatory increases in glycolysis have been hypothesized to contribute to a “Warburg transition” which makes aging mammals more susceptible to cancer. Global overexpression (OE) in mice of PTEN, an antagonist of the INS/PI3K/AKT pathway, shifts metabolism to favor oxidative phosphorylation over glycolysis and extends lifespan of male and female mice. Our unpublished work has found: (1) PTEN OE enhances chaperone-mediated autophagy (CMA); (2) In a CMA-dependent manner, PTEN negatively regulates proteins involved in glycolysis (PKLR and TKFC), and proteins that drain mitochondria of TCA cycle metabolites aketoglutarate and citrate to generate cytoplasmic acetyl-coA (IDH1 and ACLY); (3) a decrease in the hepatic abundance of these acetyl-coA and glycolysis enzymes is common to several longlived mouse models. These data suggest the hypothesis that enhanced CMA, downstream of PTEN, promotes a shift in energy production to favor oxidative phosphorylation over glycolysis by selective degradation of ACLY, IDH1, PKLR and TKFC. This hypothesis will be evaluated in two Specific Aims: (1) Characterize the mechanism through which CMA regulates the balance between glycolysis and oxidative phosphorylation, downstream of PTEN, and (2) Evaluate lysosomal targeting of glycolysis and cytoplasmic acetyl-coA enzymes in PTEN OE and PTEN KO mice. We anticipate that successful completion of this project will demonstrate an important mechanistic link between CMA and the longevity promoting PTEN transgene, providing a strong justification for future grant applications developing CMA-enhancing drugs for modulating aging.
10. Project Title: Mechanisms of Tumor Resistance in Slow-Aging Mice
  Leader: Scott Maynard, Ph.D.
  PESC Year 18 (7/1/22-6/30/23) Two major forces in the multistage cancer process are the inactivation of tumor suppressor genes and alterations in the activation state of cell receptor-mediated pathways that promote neoplasia. Studies in mice have shown that caloric restriction (CR) and certain single-gene mutations enhance lifespan and deter several age-related health changes (including cancer) by disrupting the receptor mediated pathway known as the growth hormone (GH)/insulin growth factor-1 (IGF-1) axis. However, the exact mechanisms are not known; studies suggest that the CR mice and long-lived mutant mice have both independent and shared underlying mechanisms. A shared mechanism appears to be reduced mTOR signaling, a pathway important in protein synthesis, DNA repair, autophagy and cell proliferation. This pilot grant is designed to measure skin tumor formation in mouse models that have longevity-promoting GH/IGF-1 signaling alterations, and to also process and store tumor and host cell skin samples (and plasma) for delineation of the associated mechanisms. I will use the well-established multi-stage chemical carcinogenesis mouse system in which a chemical carcinogen and inducer are applied to mouse skin to induce skin papillomas. This will be performed on three long-lived mouse models: CR mice, the Snell dwarf pituitary mutant mice, and growth hormone receptor knockout (GHRKO) mice. There are several reports of successful use of this multi-stage chemical carcinogenesis on CR mice that demonstrate that CR works to limit skin papilloma emergence, but this systems has never been performed on the GHRKO and Snell dwarf mice. The use of all three mouse models will allows us to determine to what extend the shared or independent pathway alterations work to limit tumor growth. My primary goal for the first year will be optimize the system (dosage, timing, feeding, processing of tumor/skin tissue) to display significant effects of CR, and then, with the help these optimizations, recapitulate skin tumor formation resistance in long-lived mutant mice. Various candidate biochemical and cellular processes will be measured (some in the first year) in order to determine mechanisms for altered tumor formation rates. This project will lead to long term investigations into strategies to limit carcinogenesis and to delineate cross-talk between aging and cancer pathways.
11. Project Title: Intersection of Insomnia and Centralized Pain in Older Adults: Effects on Medication Use
  Leader: Michael Smith, Pharm.D.
  PESC Year 18 (7/1/22-6/30/23) Insomnia and centralized pain are common and difficult to manage in older adults. Medications used to treat these conditions are included in the American Geriatrics Society Beers Criteria® for Potentially Inappropriate Medication (PIM) Use in Older Adults. Use of PIMs for these conditions is associated with poor outcomes, including increased risk of mortality. Our central hypothesis is that centralized pain in older adults with insomnia will confer a greater PIM burden than insomnia alone. Since both chronic pain and insomnia individually are associated with increased PIM use, it is likely that co-occurrence of these conditions would be associated with greater likelihood of PIM use. The primary objective of this pilot study is to understand medication use in the context of how increasing age mediates the interaction between insomnia and centralized pain. This will be achieved through the following Specific Aims: Aim 1: Determine the effect of age on rates of centralized pain in older adults with insomnia. H1: Increasing age will be associated with greater likelihood of centralized pain in older adults with insomnia. This quantitative aim will utilize a newly validated method (Schrepf et al. 2020) to quantify the proportion of older adults ? 55 years of age, stratified by age group, with insomnia who have co-occurring centralized pain using University of Michigan Health System Electronic Health Record (EHR) data. Aim 2: Quantify the effect of centralized pain on PIM use in older adults with insomnia. H2: Older adults with both centralized pain and insomnia will have greater PIM burden, quantified using the Drug Burden Index (DBI), than those with insomnia alone. This quantitative aim will advance the previous method using centralized pain diagnosis codes combined with a validated measure to determine the burden of anticholinergic and sedative use in older adults with insomnia and centralized pain. This study will provide a targeted population and baseline medication risk description for future intervention studies.
12. Project Title: Cross-national comparisons of disability among older adults with diabetes in 23 countries
  Leader: Shen Dewar, M.D.
  PESC Year 18 (7/1/22-6/30/23) Obesity is a growing health problem and current models of obesity care are limited in older adults. Despite the unique health care needs of older adults with obesity, currently there is no evidence-based model for this age group to manage obesity and associated disability (such as in mobility), symptoms (such as pain), multiple health issues due to long term effects of obesity (such as heart failure), and care complexity related to social determinants of health. As proof of concept, PI Dewar developed the Optimal Health, Weight, and Lifestyle (OHWL) clinic to optimize treatment of comorbid health conditions, physical function and diet in older adults with obesity. Only 1/3 of the 44 initial participants were adherent to medical specialist and therapist referrals. The remaining patients faced challenges such as lack of support for adherence to lifestyle change, low self-efficacy, and poor linkage to community resources. To address these barriers, a more comprehensive OHWL Program is proposed that features three primary components: 1) an OHWL Care Provider (oriented to obesity-centered older adult care); 2) an OHWL care manager (to assess and guide the custom intervention); and 3) a social worker to provide linkage to community resources as well as caregiver support/education. The goal of this PESC pilot is to test the feasibility and preliminary outcomes of this new model of care for older adults with obesity. In older adults (n=40, aged ?60) with obesity (BMI?35), and at least 2 obesity related comorbidities, aims in this PESC pilot are to: 1) Evaluate extent of changes in key quantitative outcomes (such as mobility and pain); and 2) Conduct a mixed methods process evaluation, guided by the RE-AIM model, of program feasibility, barriers and facilitators. The goal of the OHWL Program is to promote a patient-centered model of care to improve the functioning and quality of life of older adults with obesity, especially those from vulnerable populations who face barriers to lifestyle change. These pilot data will inform the creation of materials for a larger NIA-funded trial to be led by PI Dewar and mentors Alexander and Janevic as MPIs, to demonstrate scalability, efficacy, and costeffectiveness of this new model.
13. Project Title: Establishment of aged microbiota in germ free mice
  Leader: Vincent Young, M.D., Ph.D.
  LAC Year 17 (7/1/21-6/30/23) *RAPID PILOT* The normal microbe populations of the gut contribute to fostering immune system maturation, digestion assistance, and protection against pathogen invasion. Many age-associated conditions such as cardiovascular disease, cancer, and diabetes have been associated with abnormal host-microbe interactions. Elderly individuals are also moresusceptible to Clostridiodes difficile with an increased risk of developing disease- related complications. We are specifically interested in understanding how age-relatedchanges in the microbiota affect the outcomes of infection with Clostridioides difficile.
14. Project Title: Inflammation and the risk for cognitive decline and dementia after COVID-19
  Leader: Natalie Tronson, Ph.D.
  PESC Year 17 (7/1/21-6/30/22) Illness and stress are common risk factors for age-related cognitive decline, Alzheimer's Disease, and other dementias, likely via activation of neuroimmune inflammatory pathways in the brain. This has been difficult to study, however, because altered neuroinflammation is also a consequence of aging and of neurodegeneration. We have recently developed a mouse model within which to study the persistent consequences of immune challenge on memory, and in this project propose to apply this model to understand how transient illness during midlife increases risk for later, age-related cognitive decline, memory impairments, and dementia. Here, we will develop modified protocols to specifically examine COVID-19-like inflammatory pathways on memory across adulthood. COVID-19 is of particular relevance for cognitive decline and dementias because, unlike other illnesses including influenza, many patients experience a post-acute COVID-19 syndrome that includes memory impairments and "brain fog". Given the immense number of people affected by COVID-19, the pandemic is likely to dramatically increase the number of people impacted by age-related cognitive decline and dementias in the years to come. Here, we will determine whether and how single-stranded RNA (ssRNA)-viral mimic triggered inflammation accelerates aging-related cognitive decline in males and females long after resolution of illness.
DEVELOPMENT PROJECTS (2 Development Projects Listed)
1. Project Title: Software tools for separable covariance models in multivariate longitudinal data/repeated measures analysis
  Leader: Andrzej Galecki; Julie Bynum
  Core(s): Design, Data, and Biostatistics Core (DDBC)
  Software tools for separable covariance models in multivariate longitudinal data/repeated measures analysis
2. Project Title: Develop a real time sensor to detect hyponatremia
  Leader: James Ashton-Miller
  Core(s): Biomechanics (Biomechanics)

Develop a real time sensor to detect hyponatremia

RESEARCH (28 Projects Listed)
  Leader(s): MILLER, RICHARD A
    PAUL F. GLENN FOUNDATION / ( 2018 - 2022 )
  This project will focus on exploiting and expanding the growing evidence that drugs can slow aging and postpone diseases in animal models. The Center's activities will be directed towards three linked aims: (1) using simple model systems to rapidly identify and characterize new compounds that target evolutionarily conserved pathways that control aging; (2) facilitating the process by which candidate drugs are selected for longevity testing in mice; and (3) discovering the mechanisms by which drugs that extend lifespan achieve their effects. The central theme will be that learning how to slow aging in model systems will lead to breakthrough discoveries in our understanding of what times aging and how aging times the diseases of older adults, and that these breakthroughs, in turn, will lead to the development of practical anti-aging medications that postpone human diseases and extend healthy human lifespan.
2. Project Title: AZD1222 Vaccine Trial: A Phase III Randomized, Double-blind, Placebo-controlled Multicenter Study in Adults to Determine the Safety, Efficacy, and Immunogenicity of AZD1222, a Non-replicating ChAdOx1 Vaccine for the Prevention of COVID-19
  Leader(s): LUGOGO, NJIRA
    ASTRAZENECA PLC / ( 2020 - 2023 )
  The University of Michigan is a site for this clinical trial and 200 subjects are anticipated for the Main Study, 70 are anticipated for the Sub-Study and 20 are anticipated for the Illness Visits. The aim of the study is to assess the safety, efficacy, and immunogenicity of AZD1222 for the prevention of COVID-19. The COVID-19 pandemic has caused major disruption to healthcare systems with significant socioeconomic impacts. Currently, there are no specific treatments available against COVID-19 and accelerated vaccine development is urgently needed. A safe and effective vaccine for COVID-19 prevention would have significant public health impact.
3. Project Title: LongROAD Study: Multicenter observational study of older drivers and the impact of health, function, and technology on changes in driving behavior
  Leader(s): SILVEIRA, MARIA
  The overall goal is to generate empirical evidence for understanding the dynamics, mechanisms, determinants and consequences of mobility in senior drivers and for developing effective interventions to ensure safe mobility for older people.
4. Project Title: The Relationship between Overall Health and Gut/Skin/Oral Microbiome in Healthy Middle-aged Adults
    ACCESS BUSINESS GROUP LLC / ( 2021 - 2022 )
  To examine the relationship between the gut/oral/skin microbiome and the overall health of 60 individuals participated in the original protocol.
5. Project Title: Transfer Trauma in Nursing Home Long-Term Care Residents
  Leader(s): MONTOYA, ANA
    DONAGHUE FOUNDATION / ( 2020 - 2022 )
  Our main research question is are there adverse consequences of facility transfers among nursing home residents that can be measured and monitored prospectively to prevent transfer trauma in the future.
6. Project Title: ENHANCE: Developing a Clinical Geography Tool to Intervene in Cognitive Decline through Neighborhood Design
    NIH F32AG064815 / ( 2020 - 2022 )
  Although the majority of Americans with Alzheimer s disease and related dementias (ADRD) live independently, the neighborhood contexts in which they develop and navigate cognitive impairment are largely ignored. Environmental factors may significantly increase the risk of or buffer against ADRD, yet strategies to address cognitive decline to date largely overlook the role of neighborhoods. Residence in advantaged neighborhoods may promote cognitive functioning and/or buffer against dementia in part through greater density of physical and social resources (e.g., recreation centers, parks, libraries, coffee shops) that benefit cognitive reserve and maintain mental function through physical activity, mental stimulation, and social engagement. This project proposes to develop the new niche of clinical geography by translating geographic knowledge into a preliminary tool designed to facilitate place-based interventions that maintain and improve cognition among aging residents. First, the project aims to identify built and social environmental factors linked to changes in cognitive function over time and the onset of cognitive impairment based on secondary data analysis of a national, racially diverse, population-based sample. The dataset includes multiple measures of cognitive function and residential geographic coordinates for 30,000+ aging Americans tracked annually since 2003. Interpretations of longitudinal generalized linear mixed models will focus on identifying environmental factors relevant to trajectories of cognitive decline and onset of cognitive impairment. Second, the project aims to translate this knowledge into a preliminary diagnostic tool: Environmental Neighborhood Health Assessment to Nurture Cognitive Enhancement (ENHANCE). A community advisory board (CAB) will be formed to develop ENHANCE through diverse input from gerontologists, ADRD experts, dementia community advocates, urban planners, and older adults. The CAB will discuss how environmental factors can impact cognitive decline, develop the tool, and refine ENHANCE based upon preliminary feasibility and pilot testing. The F32 fellowship will facilitate Dr. Finlay s career development and future as a successful independent health researcher. It complements and extends her expertise in health geography and environmental gerontology through mentored training in five new areas: 1) advanced quantitative analysis; 2) cognitive function and ADRD; 3) clinical observation of cognitive impairment; 4) tailored design of environmental audits; and 5) NIH grant skills. The interdisciplinary and supportive training environment at the University of Michigan provides a foundation for Dr. Finlay to pursue translational research throughout her career. Her long-term research objective is to develop a new concept of cognability (a measure of how supportive an area is to cognitive functioning and how it buffers against cognitive impairment) with a reliable and efficient instrument to evaluate relevant macro and micro environmental conditions. Resulting tailored, place-specific interventions are intended to help aging individuals reduce risk for cognitive impairment and ADRD, live independently longer, and lessen need for long-term care.
    NIH K01AG054615 / ( 2017 - 2022 )
  ABSTRACTOsteoarthritis (OA), a debilitating age-related disease associated with pain, stiffness and poor functioning is amajor risk factor for mobility disability. Although early osteoarthritic changes within the joint commence duringmid-life (40-65 years of age), early detection of disease is limited given the lack of robust and reliable OAbiomarkers. Currently detection relies upon costly imaging modalities. Late detection of OA compromises theopportunity for early intervention and prevention of disease progression, leaving only symptom managementor, ultimately, joint replacement as strategies for treatment. Recent evidence and scientific appreciation thatunderlying metabolic dysfunction is a risk factor for osteoarthritis incidence and progression suggests thatbiomarkers which identify individuals with disordered metabolism may be relevant for subclinical markers ofOA. Metabolomics, a newly evolving field, analyzes small molecules (metabolites) in biological specimens.Metabolomics analysis has successfully identified novel biomarkers for diagnosis, monitoring and treatment forage-related diseases such as prostate cancer, diabetes and stenosis and autoimmune diseases such asrheumatoid arthritis. A small but growing number of studies in animal and human populations have reportedthat metabolomics yields potential biomarkers with good discrimination between OA patients and normalcontrols including metabolites associated with collagen, branched chain amino acid, energy, and tryptophanmetabolism. However, no studies to date have neither used metabolomics to identify biomarkers for OAincidence nor evaluated biomarkers among individuals matched for age and body size. We propose to conducta metabolomics analysis of osteoarthritis risk within the longitudinal Michigan Study of Women's HealthAcross the Nation (MI-SWAN). Specifically, 63 MI-SWAN women who developed radiographic knee OAduring follow-up will be age- and BMI-matched with 63 MI-SWAN women who remained OA-free during follow-up. Banked plasma specimens from baseline (when all subjects were OA-free) will be used to conductmetabolomics analyses using the targeted lipids eicosanoids platform (Aim 1) which includes profiles from28 eicosanoids, the lipidomics platform (Aim 2) which profiles lipids from over 10 classes including 431unique lipid species, and an untargeted platform (Aim 3) which profiles at least 250 known compounds toidentify candidate biomarkers for knee osteoarthritis risk. Relative quantitation of these metabolites will becompared within the matched pairs of women who did and did not develop incident knee OA during follow-up.This K01 award will provide needed training and skill development in metabolomics, the associatedbioinformatics considerations, and translation to clinical care and yield preliminary data to support thesubmission of an R01 application. This training will enable the candidate to develop as an independentinvestigator providing leadership in the application of metabolomics research in aging with the long-term goalof applying this approach to identify key metabolic pathways involved in aging and the disablement process.
    NIH K01AG054615 / ( 2017 - 2022 )
  ABSTRACT Osteoarthritis (OA), a debilitating age-related disease associated with pain, stiffness and poor functioning is a major risk factor for mobility disability. Although early osteoarthritic changes within the joint commence during mid-life (40-65 years of age), early detection of disease is limited given the lack of robust and reliable OA biomarkers. Currently detection relies upon costly imaging modalities. Late detection of OA compromises the opportunity for early intervention and prevention of disease progression, leaving only symptom management or, ultimately, joint replacement as strategies for treatment. Recent evidence and scientific appreciation that underlying metabolic dysfunction is a risk factor for osteoarthritis incidence and progression suggests that biomarkers which identify individuals with disordered metabolism may be relevant for subclinical markers of OA. Metabolomics, a newly evolving field, analyzes small molecules (metabolites) in biological specimens. Metabolomics analysis has successfully identified novel biomarkers for diagnosis, monitoring and treatment for age-related diseases such as prostate cancer, diabetes and stenosis and autoimmune diseases such as rheumatoid arthritis. A small but growing number of studies in animal and human populations have reported that metabolomics yields potential biomarkers with good discrimination between OA patients and normal controls including metabolites associated with collagen, branched chain amino acid, energy, and tryptophan metabolism. However, no studies to date have neither used metabolomics to identify biomarkers for OA incidence nor evaluated biomarkers among individuals matched for age and body size. We propose to conduct a metabolomics analysis of osteoarthritis risk within the longitudinal Michigan Study of Womens Health Across the Nation (MI-SWAN). Specifically, 63 MI-SWAN women who developed radiographic knee OA during follow-up will be age- and BMI-matched with 63 MI-SWAN women who remained OA-free during follow- up. Banked plasma specimens from baseline (when all subjects were OA-free) will be used to conduct metabolomics analyses using the targeted lipids eicosanoids platform (Aim 1) which includes profiles from 28 eicosanoids, the lipidomics platform (Aim 2) which profiles lipids from over 10 classes including 431 unique lipid species, and an untargeted platform (Aim 3) which profiles at least 250 known compounds to identify candidate biomarkers for knee osteoarthritis risk. Relative quantitation of these metabolites will be compared within the matched pairs of women who did and did not develop incident knee OA during follow-up. This K01 award will provide needed training and skill development in metabolomics, the associated bioinformatics considerations, and translation to clinical care and yield preliminary data to support the submission of an R01 application. This training will enable the candidate to develop as an independent investigator providing leadership in the application of metabolomics research in aging with the long-term goal of applying this approach to identify key metabolic pathways involved in aging and the disablement process.
    NIH K01AG062754 / ( 2020 - 2024 )
  This K01 application proposes career development and research activities customized to facilitate the candidates (Dr. Noah Webster) transition from conducting basic social science research to behavioral intervention research. The candidates long-term career goals include becoming an independent research scientist conducting research aimed at: a) improving the health and independence of older adults; and b) reducing later life health disparities. This will involve developing, testing, implementing, and disseminating a social network-based intervention to improve participation in behavioral health (e.g., physical activity) interventions within low resource settings. Career Development/Training Aims: In order to accomplish career goals the candidate is in need of targeted and interdisciplinary training in: 1) intervention development; 2) intervention evaluation; and 3) objective assessment of physical activity. This training will be facilitated through coursework and interactions with an interdisciplinary mentoring team led by Dr. Neil Alexander. Training Environment: The candidate is situated within the largest academically-based social science institute in the world. The resources available to him at the Institute for Social Research as well as the University of Michigans Schools of Medicine and Public Health together offer an unparalleled supportive and stimulating environment for conducting research at the intersection of social science and intervention research. Research Aims: While only 16% of people age 65+ engage in recommended physical activity levels, increases may be achieved through activation of social resources. A social network-based approach that systematically identifies and involves influential agents of change in a community is proposed to facilitate physical activity-related information dissemination and behavior change. This project will leverage Go4Life, NIAs evidence-based physical activity campaign and capitalize on the strength of social ties. The intervention addresses socio- economically linked health disparities by developing the intervention for use in affordable (HUD subsidized) senior housing. The project will address three specific aims: Aim 1) Identify agents of change in an affordable senior housing community who will then be invited to form a committee to disseminate Go4Life materials through planning, publicizing, and participating in community-wide activities over 12 months. Aim 2) Evaluate intervention feasibility using a mixed methods approach. Aim 3) Establish preliminary network effect on changes in physical activity and identify influential network mechanisms. The proposed feasibility study is the first step in using locally available and low-cost resources to affect behavior change among socio-economically vulnerable senior housing residents. In the short-term, findings will provide preliminary data to conduct a multi- site efficacy trial which will implement and evaluate successful components of the intervention. In the long- term, understanding how to leverage social networks to promote and sustain increases in physical activity will provide key information to advance the science of behavior change as well as reduce health disparities.
  Leader(s): WEI, MELISSA
    NIH K23AG056638 / ( 2017 - 2022 )
  Project Summary / AbstractMultimorbidity, the coexistence of multiple chronic conditions, poses a major and growing challenge to agingadults, their families, and healthcare systems. Most older adults have multiple chronic conditions that interactto profoundly affect physical functioning and health-related quality of life. Despite this, critical gaps remain inthe measurement of multimorbidity. In particular, there are few practical tools to guide clinicians, researchers,and policymakers who seek to improve the care for older adults. Current measures for multimorbidity haveused mortality, healthcare cost, and utilization, but have not focused on patient-centered outcomes to quantifyburden of disease. Statistical limitations in traditional methods to measure disease interactions beyond simpletwo-way disease interactions have also hampered our epidemiologic understanding of multimorbidity and itsfull impact on health and functional outcomes. To bridge these gaps, this proposal aims to 1) Develop andvalidate a new multimorbidity index for use in ICD-coded conditions; 2) Refine the multimorbidity index byincorporating multiple-order disease interactions and determine the incremental value of their inclusion; and 3)Assess the utility of the multimorbidity index through its association with key functional outcomes includingphysical and cognitive performance, basic and instrumental activities of daily living, depression, and mortality.The proposed studies will use unique data linkages between patient-reported outcomes in the nationally-representative Health and Retirement Study and Medicare claims to develop and internally validate amultimorbidity index for International Classification of Diseases (ICD)-coded chronic conditions weighted tophysical functioning. Novel approaches to data shrinkage techniques will be used to select significantinteractions among multiple potential disease combinations associated with physical functioning. The utility ofthe multimorbidity index will be assessed through its prospective associations with physical and cognitiveperformance, basic and instrumental activities of daily living, and mortality. The successful completion of thesestudies will yield a validated multimorbidity measure that captures the impact of coexisting chronic diseases onphysical functioning in older adults relevant for clinical care, research, and policy.Through this award, the candidate will achieve immediate career goals to gain new specialized skills in usingadministrative claims, ICD coded data, and novel statistical approaches to high-dimension data, and achieve adeeper understanding of measuring key health outcomes in older adults with multimorbidity. The facilities,sponsoring department, and intellectual resources at the University of Michigan provide an exceptional milieufor this career development award and Early Stage Investigator. The training and professional developmentacquired through this award will contribute to the candidate's long-term goal to be an independent clinician-investigator focused on improving the management, quality of care, and prognosis of vulnerable older adultswith multimorbidity.
11. Project Title: Ectonucleotidase modulation of age-dependent vascular calcification and stiffness
    NIH K76AG064426 / ( 2020 - 2025 )
  Abstract With increasing age, blood vessels become stiffer and more calcified. In the latter years of the human lifespan, the process of vascular aging accelerates. The reason that blood vessels lose their youthful elasticity and ability to retard the deposition of calcium precipitously later in life is poorly understood. Ectonucleotidases are found on the surface of endothelial cells which line the inner surface of blood vessels, vascular smooth muscle cells, and leukocytes. The ectonucleotidase CD39 is responsible for cleaving ATP and ADP to form AMP, and subsequently, CD73 is responsible for generating adenosine from AMP. Since ATP and ADP are pro- inflammatory and act in a paracrine fashion, I hypothesize that ectonucleotidase activity plays a role in the vascular stiffness and calcification that occurs as a consequence of age. This is supported by my preliminary data in wild type (C57BL/6) mice, which demonstrates CD73 protein levels declined with age (up to 24 months) in the heart and kidney. This is also supported by preliminary data in mice and human tissues demonstrating that loss of CD73 expression promoted expression of the transcription factor Runx2, which is critical for osteogenesis. We hypothesize that loss of ectonucleotidase expression with age could have deleterious consequences on the vessel wall, resulting in an environment which promotes vascular calcification and stiffness. Since the role of ectonucleotidases in vascular aging is unknown, we will elucidate mechanisms which mediate age-dependent vascular calcification through the following aims. Aim 1: We will determine how age-dependent decline in vascular ectonucleotidase expression renders vessels susceptible to vascular calcification and fibrosis in a murine model. Aim 2: We will determine how ectonucleotidase activity mitigates arterial fibrosis and stiffness. Aim 3: We will determine if ectonucleotidase expression plays a role in age-driven human coronary artery calcification. Achievement of these aims will elucidate the role of ectonucleotidases in age-dependent vascular calcification and stiffness in mice and humans. The mechanistic insights obtained from these experiments will define my future investigative direction and serve as a foundation for a subsequent RO1 application as an independent investigator studying vascular biology and aging.
12. Project Title: Multicenter clinical trial of telehealth vs. in-person delivery of palliative care to Stage IV lung cancer patients
  Leader(s): SILVEIRA, MARIA
    PCORI PLC-1609-35995 / ( 2018 - 2024 )
  Early and longitudinal involvement of palliative care (PC) in the outpatient management of patients with advanced cancer improves patient-reported and end of life (EOL) care outcomes. While recommended by national organizations as the standard of care, this early integrated care model utilizes substantial PC resources, which has limited its dissemination across care settings. Telehealth (i.e., the use of information and communication technology in health care delivery) is an effective strategy to increase patients access to health care services when the numbers of specialty-trained clinicians are limited. We seek to perform a multi-site comparative effectiveness trial of early integrated telehealth versus in-person PC in patients with advanced lung cancer. By demonstrating the equivalence of the telehealth delivery modality, we seek to define a role for this more accessible, scalable and patient-centered approach to PC.
13. Project Title: Decision Making for Cardiovascular Therapy in Adults with Mild Cognitive Impairment
  Leader(s): LEVINE, DEBORAH
    NIH R01AG051827 / ( 2016 - 2022 )
  DESCRIPTION (provided by applicant): There is a fundamental gap in understanding how mild cognitive impairment (MCI) influences treatment and decision making for serious illnesses, like cardiovascular disease (CVD), in older patients. Poor understanding of clinical decision making is a critical barrier to the design of interventions to improve the quality and outcomes of CVD care of in older patients with MCI. The long-term goal of this research is to develop, test, and disseminate interventions aimed to improve the quality and outcomes of CVD care and to reduce CVD-related disability in older Americans with MCI. The objective of this application is to determine the extent to which people with MCI are receiving sub-standard care for the two most common CVD events, acute myocardial infarction (AMI) and acute ischemic stroke, increasing the chance of mortality and morbidity in a population with otherwise good quality of life, and to determine how MCI influences patient preferences and physician recommendations for treatment. AMI and acute ischemic stroke are excellent models of serious, acute illnesses with a wide range of effective therapies for acute management, rehabilitation, and secondary prevention. Our central hypothesis is that older adults with MCI are undertreated for CVD because patients and physicians overestimate their risk of dementia and underestimate their risk of CVD. This hypothesis has been formulated on the basis of preliminary data from the applicants' pilot research. The rationale for the proposed research is that understanding how patient preferences and physician recommendations contribute to underuse of CVD treatments in patients with MCI has the potential to translate into targeted interventions aimed to improve the quality and outcomes of care, resulting in new and innovative approaches to the treatment of CVD and other serious, acute illnesses in adults with MCI. Guided by strong preliminary data, this hypothesis will be tested by pursuing two specific aims: 1) Compare AMI and stroke treatments between MCI patients and cognitively normal patients and explore differences in clinical outcomes associated with treatment differences; and 2) Determine the influence of MCI on patient and surrogate preferences and physician recommendations for AMI and stroke treatment. Under the first aim, a health services research approach- shown to be feasible in the applicants' hands-will be used to quantify the extent and outcomes of treatment differences for AMI and acute ischemic stroke in older patients with MCI. Under the second aim, a multi-center, mixed-methods approach and a national physician survey, which also has been proven as feasible in the applicants' hands, will be used to determine the influence of MCI on patient preferences and physician recommendations for AMI and stroke treatment. This research proposal is innovative because it represents a new and substantially different way of addressing the important public health problem of enhancing the health of older adults by determining the extent and causes of underuse of effective CVD treatments in those with MCI. The proposed research is significant because it is expected to vertically advance and expand understanding of how MCI influences treatment and decision making for AMI and ischemic stroke in older patients. Ultimately, such knowledge has the potential to inform the development of targeted interventions that will help to improve the quality and outcomes of CVD care and to reduce CVD-related disability in older Americans.
14. Project Title: Regional genomic epidemiology to identify drivers of resistance, transmission and infection with carbapenem-resistant Klebsiella pneumoniae
  Leader(s): SNITKIN, EVAN
    NIH R01AI148259 / ( 2020 - 2024 )
  The emergence and worldwide dissemination of antibiotic resistant organisms represents a significant threat to global public health. An organism that epitomizes both the urgency and challenges associated with this threat is carbapenem-resistant Klebsiella pneumoniae (CRKP). CRKP was first observed in a clinical case in 1996 in a hospital in North Carolina. Since that time, successful lineages of CRKP have spread across the globe, becoming endemic in healthcare networks in many regions. This increasing prevalence of CRKP poses a great risk to hospitalized patients, as crude mortality rates for CRKP infections can be upwards of 50%. Moreover, the threat associated with CRKP continues to escalate, with numerous reports of CRKP that are resistant to even last-line antibiotics, leaving affected patients with limited treatment options. The seriousness of the CRKP epidemic has led to both the U.S. Centers for Disease Control and the World Health Organization ranking it as their most urgent antibiotic resistant threat. However, despite the attention given to CRKP, it remains highly prevalent in many areas. Our central hypothesis is that our inability to effectively control CRKP, as well as other urgent antibiotic resistant threats, is due to a lack of understanding of the clinical and epidemiologic factors that drive the emergence and spread of antibiotic resistant organisms across regional healthcare networks. Here, we seek to overcome this knowledge gap by first applying whole-genome sequencing to construct regional transmission networks for CRKP, and then overlaying rich epidemiologic and clinical meta-data to identify drivers of transmission, resistance evolution and infection across regional healthcare facilities. These goals will be accomplished through the following three aims: 1) apply phylogenetic methods to reconstruct regional transmission networks, and perform data analysis and modeling to identify drivers of transmission within and between hospitals, 2) identify genetic determinants of resistance to last line antibiotics and analyze in the context of the regional transmission network and clinical metadata to identify factors associated with both the evolution and acquisition of resistance and 3) identify genetic determinants associated with CRKP infection and analyze in the context of the regional transmission networks and patient meta-data to identify virulent sub-lineages and convergent variation that are associated with poor patient outcomes. The totality of these aims will provide critical insight into the factors driving transmission, resistance evolution and infection with CRKP as it spreads across regional healthcare networks. Moreover, we believe our approach of integrating genomic, clinical and epidemiologic data to study the proliferation of antibiotic resistant threats at a regional level can be applied in other contexts to help guide regional infection prevention.
15. Project Title: Leveraging large-scale national data to understand, reduce, and prevent benzodiazepine-related harms among older adults
  Leader(s): MAUST, DONOVAN T
    NIH R01DA045705 / ( 2018 - 2023 )
  Benzodiazepine (BZD) use in the U.S. is common and increases with age. In a recent analysis, 8.7% of adults aged 65-80 years were prescribed BZDs during one year, even though a robust set of studies have established their association with a variety of adverse outcomes in older adults, including increased risk of falls and fractures, motor vehicle accidents, impaired cognition, and pharmaceutical overdose. Patients and their providers are then reluctant to change use once started, which may account for why older adults experience the highest rates of long-term BZD use. Relatively little is known about the patient, provider, and community characteristics associated with starting and continuing BZD prescribing to older adults, yet this is critical to develop effective selective and indicated prevention strategies. In Aim 1, we will describe the patient, provider, and community characteristics associated with BZD initiation and continuation using a national 20% sample of Medicare beneficiaries (n=3.6 million) linked to provider data from the American Medical Association (AMA) Physician Masterfile and community characteristics from the Area Health Resources File (AHRF). We will extend our analysis with OptumInsight data (n=6.7 million) to gain additional insights among commercially insured adults aged 50-64 given increased substance use among the Baby Boom cohort. Those patients currently prescribed BZDs and most at risk for BZD misuse (e.g., overlapping BZD prescriptions from multiple providers) and BZD-related overdose should receive indicated prevention strategies to address this potentially harmful use. In Aim 2, among those prescribed BZD, we will determine specific risk factors associated with BZD misuse and BZD-related overdose; these data will be used to develop a misuse clinical prediction tool. Using BZD users 50+ years old identified in Medicare and Optum, we will determine characteristics of patients and their prescribed BZD (e.g., high potency) most associated with misuse and overdose. We will then use machine learning to create a simple clinical prediction tool that providers can use to identify older adults at risk for misuse in their practices. Finally, in Aim 3 we will conduct semi-structured interviews with providers and patients to package and script the use of the clinical prediction tool for providers seeking to engage high-risk BZD use patients. This aim is critical to improve the impact of our findings since psychological dependence on BZD can make reducing use a difficult topic for physicians and patients to address. We will conduct interviews with providers and older adult primary care patients (n=15 each) to obtain feedback to package and script the use of the clinical prediction tool, which we will make publicly available by website. The impact of our work will be to: 1) provide a detailed, national portrait of the factors that contribute to BZD use and misuse; 2) determine the older adults most at risk for serious adverse events; and 3) develop and package a clinical prediction tool to help providers address BZD use in their high-risk patients.
16. Project Title: Understanding the role of the Complement Proteome in progressive Diabetic Kidney Disease
    NIH R01DK123459 / ( 2020 - 2025 )
  PROJECT SUMMARY / ABSTRACT There is a critical need to identify novel mechanisms of diabetic kidney disease (DKD) that will provide targets for new interventions. Chronic inflammation is one plausible mechanism. Using untargeted high-throughput aptamer proteomics, our recently published study has shed new light on specific, key inflammatory drivers of DKD. This was a large prospective three-cohort study that identified a novel and extremely robust circulating signature (KRIS) associated with risk of ESRD in diabetes. Our pilot study points to the data-driven connection between circulating KRIS and urinary profiles of the Complement pathway. Our hypothesis is that the Complement involvement in the kidney is a downstream effect of the systemic inflammatory processes mediating an increased DKD risk. The overarching goal of this proposal is to provide a high-resolution view of the involvement of the Complement proteome in progressive diabetic kidney disease. Aim 1 will comprehensively evaluate the etiological role of the urinary Complement proteome in progressive DKD leading to ESRD. This evaluation will leverage a prospective two-cohort population of Joslin Kidney Study (JKS) participants with an overt DKD at baseline followed for 10 years (primary outcome incident ESRD). Measurements will utilize an aptamer proteomic technology (SOMAscan). Aim 2 will extend generalizability of the urinary Complement proteome to earlier DKD stages. The proposed study will be conducted in participants of the Preventing Early Renal Loss (PERL) clinical trial with predominantly normal renal function at baseline followed for 3 years (primary outcome - renal slope). Aim 3 proposes to gain direct insight into the intra-renal Complement proteome by targeted and untargeted protein studies in diabetic kidney tissue (Susztaklab Biobank). This project focuses on a significant public health problem, leverages the progressiveness of the disease, employs an innovative proteomic technology and stems from strong preliminary data. Advances in this project will pinpoint missing key components of DKD etiology, thereby accelerating drug development strategies for patients with diabetes.
17. Project Title: Kidney Tubular Functions in Type 1 Diabetes
    NIH R01DK125084 / ( 2020 - 2024 )
  ABSTRACT Chronic kidney disease is a common and serious complication of type 1 diabetes (T1D). Historically, diabetes has been viewed as a primary glomerular kidney disorder based on classic pathological features. However, diabetes also promotes injury to kidney tubular epithelial cells and their microenvironment through increased work of glucose reabsorption and direct stimulation of pro-inflammatory and pro-fibrotic pathways. Sodium glucose co-transporter-2 inhibitors, which block glucose entry into proximal tubular cells, are the most promising new treatment for slowing the progression of kidney disease in type 2 diabetes. Compelling mechanisms of kidney tubular injury in diabetes have been incompletely translated into human disease, impeding new strategies for monitoring and treatment. The goal of this proposal is to advance understanding of the evolution, determinants, and clinical consequences of kidney tubular functions in persons with type I diabetes (T1D). We will add novel measurements of tubular functions and damage to two landmark clinical trials of T1D spanning the course of kidney disease. Through these measurements, we will for the first time characterize the natural history of tubular functions over time in T1D, identify potential risk factors for the loss of tubular functions, and test whether measures of tubular functions and damage are associated with metabolic complications, changes in key pathologic features, and a decline in glomerular kidney functions. The construction of a detailed natural history of kidney tubular functions in T1D will lay needed groundwork for the future development of new interventions to improve prevention, monitoring, and treatment.
18. Project Title: Skeletal Health in Type 1 Diabetes and the Role of Diabetic Kidney Disease
    NIH R01DK125646 / ( 2020 - 2024 )
  PROJECT SUMMARY/ABSTRACT Type 1 diabetes (T1D) is associated with increased risk of fracture throughout the lifespan. As individuals with T1D now live to older ages, when morbidity and mortality from fracture are greatest, it is crucial to understand this skeletal fragility and identify strategies to mitigate fracture risk. Bone mineral density is reduced, but fracture is elevated out of proportion to this reduction, indicating that other factors bone quality also contribute to the skeletal fragility. These may include low bone turnover and compromised bone geometry and microstructure. The presence of a diabetes microvascular complication is associated with particular skeletal fragility, but studies to date have been unable to disentangle specific contributions of each complication, nor to determine whether associations are independent of glycemic control. Of the microvascular complications, diabetic kidney disease may be especially detrimental, as other skeletal effects of T1D may be compounded by bone and mineral derangements of chronic kidney disease, including abnormal bone turnover and vitamin D metabolism. Our central hypothesis is that diabetic kidney disease particularly affects the already vulnerable T1D skeleton and plays a key role in the pathophysiology of diabetic skeletal fragility. The PERL trial presents a unique opportunity to understand the overlapping impact of these effects, as it has extensively characterized the kidney function of adult participants with T1D and diabetic kidney disease of varied severity. This 3-year trial of the effects of allopurinol vs. placebo on kidney function has ended, and participants are enrolled in an observational post-trial cohort study. In the 148 participants at 7 PERL centers, we propose an ancillary study that will add skeletal imaging for bone density (with dual-energy X-ray absorptiometry) and bone microstructure and estimated strength (with high-resolution peripheral quantitative computed tomography). We will also add analyses on stored serum specimens from 3 time points during PERL. A subset of participants (N=25) will undergo tetracycline-labeled bone biopsy. We will estimate relationships of gold-standard iohexol GFR and albuminuria measured longitudinally with skeletal parameters (Aim 1a). Then, we will determine if those relationships vary across a wider spectrum of kidney function, by combining data from PERL with consistently-acquired skeletal imaging data from 220 adults in the EDIC study, many of whom have normal GFR and no albuminuria (Aim 1b). We will next determine if glycemic control is independently associated with skeletal parameters in PERL (Aim 2). Finally, we will examine whether high or low parathyroid hormone and bone turnover marker levels are associated with skeletal parameters, and whether altered vitamin D metabolites partially explain the kidney-bone relationship (Aim 3). In the biopsy subset, we will explore whether PTH and bone turnover markers correlate with histomorphometric turnover. This research has the potential to shape the care of patients with T1D by informing screening approaches and interventions. Ultimately, it could help reduce fracture risk in our aging T1D population.
19. Project Title: Development of Prognostic Algorithms to Identify Subjects at High Risk of ESKD in Type 2 Diabetes
    NIH R01DK126799 / ( 2021 - 2025 )
  PROJECT SUMMARY/ABSTRACT With the rising prevalence of diabetes in the US and other countries, there is an ongoing research effort to find biomarkers allowing the identification of patients with diabetes at high risk of end stage kidney disease (ESKD). With support from NIH and JDRF, we have identified 21 serum proteins that were significantly associated with increased risk of kidney function loss and ESKD in the Joslin Kidney Study, and have developed an ad hoc OLINK multiplex assay (so called Joslin Kidney Panel [JKP]) to measure these biomarkers. Preliminary data strongly suggest that a subset of the JKP can significantly improve the ability to predict ESKD risk in subjects with type 2 diabetes (T2D) when added to GFR and allbuminuria. In this proposal, we aim to validate these preliminary findings in other settings, in order to develop improved algorithms for ESKD risk prediction. We intend to accomplish these goals using existing data and specimens from individuals with and without T2D from 1. the Chronic Renal Insufficiency Cohort (CRIC) Study; and 2. the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial and its follow-up study ACCORDION. Our Specific Aims are: 1: To identify the most informative of the 21 biomarkers in the Joslin Kidney Panel and evaluate their performance, when added to GFR and albuminuria, in predicting ESKD risk among subjects with T2D and chronic kidney disease. We will measure the 21 proteins of the JKP in baseline serum specimens from ~1,500 CRIC participants with T2D, and will use these data together with GFR and albuminuria to develop and internally validate multi-marker prognostic algorithms predicting the risk of ESKD (primary outcome) or the composite of ESKD and/or 50% loss of kidney function (secondary outcome) during 10 years of follow-up. 2: To evaluate the generalizability of findings from CRIC to T2D individuals with a broader spectrum of kidney function. We will assay the JKP in baseline serum specimens from a case- cohort sample of ~2,000 ACCORD/ACCORDION participants and will use these data to investigate the generalizability of the predictive algorithms built in CRIC to diabetic patients with different characteristics. The prognostic models developed in Aim 1 and externally validated in Aim 2 will be used to build a web-based Kidney Risk Calculator for the estimation of the 10-year risk of ESKD in a clinical setting. 3: To evaluate the transferability of the Kidney Risk Calculator from diabetic to non-diabetic kidney disease. We will measure the 21 JKP biomarkers in baseline serum samples from ~1,700 non-diabetic subjects from the CRIC study and will assess the performance of the Kidney Risk Calculator developed in Aim 2 in predicting the risk of ESKD and ESKD/50% kidney function loss in patients with non-diabetic kidney disease. The proposed research has a high likelihood of resulting in the development of improved prognostic tools for the stratification of patients with diabetes according to their risk of progression to ESKD. This would be a great advancement for optimizing patient care and for improving the efficiency of clinical trials of new ESKD-preventing interventions.
20. Project Title: Early myocardial remodeling and progressive kidney function decline in type 1 diabetes
    NIH R01HL161858 / ( 2021 - 2026 )
  SUMMARY A large proportion of the excess CVD morbidity and mortality experienced by individuals with T1D occur in conjunction with diabetic kidney disease (DKD), which is associated with a striking increase in the risk of coronary artery disease (CAD) and heart failure. The latter is frequently due to the development of diabetic cardiomyopathy a diabetes-specific alteration of the myocardium. The etiologic links between DKD and cardiomyopathy are not clear, but preliminary data from our group suggest a pivotal role of the kidney function decline component of DKD rather than albuminuria. Specifically, using an MRI-derived marker of cardiomyocyte size, we have observed that patients with T1D who are losing kidney function but still have preserved GFR have subclinical signs of myocardial remodeling, as indicated by a larger cardiomyocyte size and a reduction of myocardial fiber shortening during systole as compared to T1D patients with stable kidney function. The overall goal of this collaborative proposal, which is in response to RFA-HL-21-014, is to take advantage of the latest developments in cardiac imaging and biomarker platforms to characterize the cardiac involvement in patients with T1D and DKD, focusing on the initial events in the development of diabetic cardiomyopathy. GFR Decliners (GFR loss in the previous 3-6 years =3 ml/min/year, n=100) and GFR Non- Decliners (n=100) with T1D and CKD stage 1-3A, along with Non-diabetic controls (n=100) of similar age and CKD stage, will undergo a gadolinium-enhanced cardiac magnetic resonance (CMR) and a gated cardiac CT scan to quantify coronary artery calcium (CAC). Through these studies, we will address the following Specific Aims: 1. To evaluate the presence and severity of myocardial remodeling among T1D patients and assess its relationship with early progressive kidney function decline. Cardiomyocyte size (tic) and interstitial fibrosis (measured as extracellular volume [ECV]) will be quantified by CMR and compared among GFR Decliners, GFR Non-Decliners, and Non-Diabetic subjects, and also related to albuminuria and presence and severity of CAD. 2. To assess the relative contribution of cardiomyocyte hypertrophy and interstitial fibrosis to impaired cardiac function among T1D patients. Indices of cardiac function and myocardial strain will be derived from the CMR data and evaluated for their association with cardiomyocyte size (tic) and interstitial fibrosis (ECV), in relation to the severity of concomitant CAD. 3. To gain insights into the disease processes involved in the etiology of myocardial remodeling and assess whether these overlap with those involved in the progressive kidney function decline. In targeted studies, we will focus on serum proteins implicated in heart failure or previously associated with increased risk of GFR loss. In untargeted studies, we will leverage the latest developments in multiplexed assays to evaluate serum protein profiles in a systematic fashion. With the information generated by this study on hand, we will be optimally positioned to develop new strategies and possibly new drugs to prevent CVD in T1D.
    AHRQ R01HS027431 / ( 2020 - 2024 )
  Considered one of the most urgent microbial threats by the Centers for Disease Control and Prevention (CDC), estimates of the excess costs of C. difficile infection (CDI) to the healthcare system range from $897 million to over $4 billion. Our long-term goal is to develop tools to identify patients at risk for CDI that could reduce its incidence, decrease transmission, improve patient outcomes, and reduce healthcare expenditures. We have developed and validated an algorithm using the electronic health record (EHR) to identify patients at high risk for CDI several days in advance of their diagnosis. However, there is a gap in knowledge as to whether real- world data-driven risk models can improve outcomes by guiding interventions in a clinical setting. To fill this gap in knowledge and improve CDI prevention efforts in hospitals, we propose the following specific aims: 1) to prospectively deploy an institution-specific daily risk prediction model for CDI and assess how elevated risk relates to colonization with C. difficile; 2a) to conduct a quality improvement study assessing a hospital-wide intervention bundle that incorporates patient risk for CDI; and 2b) to identify heterogeneous intervention effects across different subgroups (e.g., colonized versus not colonized; specific ribotypes) and secondary outcomes (e.g., reduced severity/complications). We will apply our model to daily extracts of EHR data, collect discarded rectal swabs and stool after standard clinical testing is completed to determine colonization status / ribotypes, and assess our model with respect to colonization status, potentially incorporating it to further improve the model. Using rates of hospital-acquired CDI, we will also assess the impact of a hospital-wide, risk-based prevention bundle rolled out for each ward in stepped-wedge, cluster- randomized fashion. The bundle will include both infection prevention and antimicrobial stewardship components. This project s successful completion would provide a model for improving the prevention of CDI and other healthcare associated infections in hospitals and health centers.
22. Project Title: The Effect of Lower Blood Pressure over the Life Course on Late-life Cognition in Blacks, Hispanics, and Whites (BP-COG)
  Leader(s): LEVINE, DEBORAH
    NIH R01NS102715 / ( 2017 - 2023 )
  Project Summary/Abstract There is a fundamental gap in understanding how racial/ethnic differences in blood pressure (BP) control influence ra- cial/ethnic disparities in cognitive impairment and dementia (CID). Poor understanding of the biological factors driving socio-demographic disparities in CID is a critical barrier to the design of interventions aimed to eliminate these dispari- ties. The long-term goal of this research is to develop, test, and disseminate interventions that prevent CID and can be ap- plied to diverse populations. The objectives of this study are to quantify the effects of racial/ethnic differences in BP con- trol on racial/ethnic differences in CID, to quantify the potential impact of optimal BP treatment intensity to reduce ra- cial/ethnic disparities in CID, and to design a feasible BP intervention trial to reduce the risk of CID or cognitive decline. CID is an excellent model of a serious, chronic illness with racial/ethnic disparities in prevalence and costs. High BP is an ideal biological risk factor because it is modifiable with a wide range of effective therapies for management. Our central hypothesis is that racial/ethnic differences in the control of high BP across the life course contribute to racial/ethnic dis- parities in late-life CID. The rationale for the proposed research is that understanding how racial/ethnic differences in BP control from young adulthood to late-life contribute to racial/ethnic disparities in CID has the potential to translate into targeted interventions aimed to improve the quality and outcomes of high BP, resulting in new and innovative approaches to the prevention of CID and other serious, chronic illnesses disproportionately affecting Blacks and Hispanics. Guided by strong preliminary data, this hypothesis will be tested by pursuing 3 specific aims: 1) Determine the influence of lower BP levels from young adulthood to late-life on CID risk in Blacks, Hispanics, and Whites; and 2) Estimate the potential impact of optimal BP treatment intensity to reduce racial/ethnic disparities in CID; and 3) Determine the sample size and duration of a trial that is adequately powered to find an effect size of BP lowering on CID that is clinically im- portant. Under Aim 1, a health services research approach with pooled cohort studies shown to be feasible in the appli- cants' hands will be used to measure the effects of BP levels and use of antihypertensive medication from young adult- hood to late-life on CID risk. Under Aims 2 and 3, a simulation modeling approach, which also has been proven as feasi- ble in the applicants' hands, will be used to quantify the individual and societal effects of eliminating racial/ethnic differ- ences in BP control from young adulthood to late-life on racial/ethnic disparities in late-life CID, and to determine the sample size and duration of a BP intervention trial to reduce the risk of CID or cognitive decline in diverse groups. This research proposal is innovative because it includes young adults and Hispanics. Not only do racial/ethnic disparities in BP control begin in young adulthood, but the effect of high BP on cognition also appears to begin in young adulthood. Hispanics are an understudied population that has greater risk of worse BP control and CID than Whites. The study will improve current BP-related risk prediction models by incorporating new population-based risk estimates from diverse co- horts and by adding CID as a BP-related outcome to an existing cardiovascular disease computer simulation model. This CID-enhanced computer simulation model will estimate the individual and societal benefits of optimal BP treatment in- tensity on CID to inform clinical care and policy and determine the sample size and duration of a BP intervention trial to reduce the risk of CID. The proposed study is significant because it will generate new knowledge and methods needed to understand the impact of racial/ethnic differences in optimal BP treatment intensity over the life course on racial/ethnic disparities in CID and to improve the design of BP lowering trials and their application to diverse populations. Ultimately, such knowledge has the potential to inform the development of targeted interventions that will help to improve the pre- vention of CID and to reduce CID-related disability in older Americans particularly minorities.
  Leader(s): CHOPRA, VINEET
    AHRQ R18HS025891 / ( 2018 - 2022 )
  Use of peripherally inserted central catheters (PICCs) for intravenous antibiotics, infusion ofchemotherapy or invasive hemodynamic monitoring has grown substantially in hospitalizedpatients. Although such use reflects advantages of PICCs (such as safer insertion in veins ofthe arm compared to veins of the neck or chest for conventional central venous catheters), notall PICCs are placed for appropriate reasons. Furthermore, PICCs are associated with importantcomplications, including venous thromboembolism (VTE) and central line-associatedbloodstream infection (CLABSI). Identifying and balancing the risks and benefits related toPICCs is critical to ensuring patient safety.The long-term objective of this study is to improve use and outcomes of PICCs across hospitalsin the United States. Supported by funding from an AHRQ K award, the PI for this proposaldeveloped the Michigan Appropriateness Guide to Intravenous Catheters (MAGIC), anevidence-based tool to inform and improve PICC use in hospital settings. This research projectnow aims to (a) implement MAGIC across 48-hospitals to determine whether it can improveappropriateness of PICCs; (b) evaluate whether improvements in PICC appropriateness areassociated with fewer complications; and (c), identify what aspects of implementation at thehospital level led to the greatest change in appropriateness and complications. The study willleverage a large Blue Cross/Blue Shield of Michigan-funded collaborative quality improvementconsortium: the Michigan Hospital Medicine Safety (HMS) consortium. Given a robustinfrastructure for data collection and 48-member hospitals all actively engaged in improvingPICC safety, HMS is the ideal setting to test MAGIC. Knowledge generated from this study willbe seminal to making healthcare safer and understanding what provider and systems factorsare associated with hospital performance both priority areas for AHRQ.This project will be the first large scale implementation of a tool that has the potential tosubstantially improve the safety of thousands of patients that receive PICCs. Exceptionalresources and team with extensive expertise in implementation science, patient safety andhealth services research make the University of Michigan an ideal environment for this proposal.
24. Project Title: Translational Geroscience Network
    NIH R33AG061456 / ( 2019 - 2023 )
  Aging is the leading risk factor for the disorders that account for the bulk of the nation's morbidity, mortality, and health costs. Recent findings suggest it is feasible to alleviate such disorders as a group by targeting fundamental aging processes. Several such interventions are near the point of entering human proof-of-concept clinical trials. Since interventions that increase lifespan and healthspan in mammals now exist, we hypothesize that clinical interventions targeting fundamental mechanisms of aging may delay, prevent, or treat age-related diseases and disabilities as a group, instead of one at a time. To accelerate testing this hypothesis, we propose a Translational Geroscience Network (TGN). Planning began 4 years ago through an NIA R24 grant involving 122 investigators in the biology of aging and clinical geriatrics. Our goal is to mature this network into a national resource starting with a subgroup of centers committed to working together using common measures and protocols allowing network-wide learning from complementary, small-scale, proof-of- concept use case clinical studies. Aim 1 is to establish a TGN to develop, implement, test, and harmonize methods and standard operating protocols (SOPs) for translational early phase trials of agents that target fundamental aging processes. The TGN will support development, coordination, and infrastructure around independently-funded use case trials (2-3 per year) using re-purposed drugs for which preclinical or clinical data already exist, such as a multicenter trial of senolytics for idiopathic pulmonary fibrosis, a trial of a different drug to reduce senescent cell burden and alleviate frailty in older women, and a trial of metformin to enhance immune responses to influenza vaccination. Based on these use case trials, we will streamline and harmonize approvals, recruitment, sample collection, SOPs, and analytic procedures across the TGN. Aim 2 is to select, optimize, and validate ancillary measures of fundamental aging processes to be assayed across all trials to establish reference analytical capabilities. An existing cell senescence assay facility will be expanded to analyze blood, other body fluids, cells, and biopsies from trials across and beyond the TGN to serve as a national resource. New assays will be developed and optimized. The facility will expand to include laboratories beyond the TGN and incorporate assays of key basic aging mechanisms, including mTOR activity, proteostasis, autophagy, mitochondrial function, and epigenetics. Aim 3 is to provide statistical and data management support to select efficient study designs, provide sample size estimates and support a TGN-wide data entry platform to facilitate cross-study comparisons. Aim 4 is to develop a biobanking and repository network for samples from the clinical trials to permit future analyses as new ancillary research questions are developed and assays become available. A system for disseminating samples to the basic biology of aging community, biobanking protocols, and operating manuals will be developed. Translating agents targeting basic aging processes into interventions for the major chronic diseases and age-related disabilities could be transformative.
25. Project Title: The Effect of Vascular Risk Factors on Risk of Alzheimer's Disease and Related Dementias after Stroke (STROKE COG)
  Leader(s): LEVINE, DEBORAH
    NIH RF1AG068410 / ( 2020 - 2024 )
  PROJECT SUMMARY/ABSTRACT Alzheimer s disease and Alzheimer s disease-related dementia (AD/ADRD) incidence is high in older adults with stroke. There is a fundamental gap in understanding how vascular risk factors (VRFs) influence risk of post-stroke AD/ADRD. Poor understanding of the biological factors driving post-stroke AD/ADRD risk is a critical barrier to the design of interventions aimed to protect the brain health of stroke survivors. The long-term goal is to develop, test, and disseminate VRF interventions that reduce post-stroke AD/ADRD for diverse populations. The study objective is to quantify how VRFs influence post-stroke AD/ADRD risk to inform preventive interventions tailored to stroke survivors and inform clinical care and policies. Post-stroke AD/ADRD is an excellent model of a serious, chronic illness of aging with high prevalence and costs. High blood pressure (BP), diabetes, and high cholesterol are ideal biological VRFs because they are common and modifiable with a wide range of effective therapies for management. Our central hypothesis is that post-stroke VRF levels contribute to post-stroke AD/ADRD. The rationale for the proposed research is that knowing the impact of VRF levels and stroke (sub)type on post-stroke AD/ADRD will improve our understanding of vascular biology and translate into new and innovative approaches for prevention of post-stroke AD/ADRD. Guided by strong preliminary data, this hypothesis will be tested through 3 specific aims: 1) Quantify the influence of post-stroke VRF levels on post-stroke cognitive trajectories and AD/ADRD, and explore how sex and race affect these relationships; 2) Clarify the relationships between stroke subtype and post-stroke cognitive trajectories and AD/ADRD, and explore how VRFs, sex, and race affect these relationships; and 3) Refine and expand an existing AD/ADRD-CVD computer simulation model by adding post-stroke AD/ADRD and results from Aims 1 and 2 to quantify the subset of stroke events, sample size, and duration of trials that are adequately powered to find clinically important and plausible effect sizes of VRF lowering on post-stroke AD/ADRD. The results of Aims 1 and 2 will be the identification of both VRF targets for interventions to reduce post-stroke AD/ADRD risk and the sub-groups of stroke survivors most likely to benefit from VRF lowering. The results of Aim 3 will be a new simulation model applicable to stroke survivors that can be used to inform clinical research trials, clinical care, and policies. This research is innovative because it will ultimately yield a novel simulation model that could provide new guidance that may change clinical practice and health policy for stroke survivors. The proposed study is significant because it will generate new knowledge and methods to understand the impact of optimal VRF treatment intensity on post-stroke AD/ADRD risk and improve the design of VRF lowering trials in stroke survivors. Ultimately, such knowledge has the potential to inform the development of targeted interventions to improve the prevention of post-stroke AD/ADRD and to reduce AD/ADRD-related disability in older Americans.
26. Project Title: Interventions Testing Program at UM
  Leader(s): MILLER, RICHARD A
    NIH U01AG022303 / ( 2003 - 2024 )
  Identification of small molecules that extend mouse lifespan provides new insights into mechanisms of longevity determination in mammals, and may lay the groundwork for eventual anti-aging therapies in humans. The NIA Interventions Testing Program (ITP) evaluates agents proposed to extend mouse lifespan by retardation of aging or postponement of late life diseases. Interventions proposed by multiple collaborating scientists from the research community are tested, in parallel, at three sites (Jackson Laboratories, University of Michigan and University of Texas), using identical, standardized protocols, and using sufficient numbers of genetically heterogeneous mice to provide 80% power for detecting changes in lifespan of 10%, for either sex, after pooling data from any two of the test sites. Seventy-two such lifespan experiments, involving various doses of 44 distinct agents, have been initiated in the first fifteen years of the ITP. Thirty-seven experiments have involved comparative tests of multiple doses of effective agents, variable starting ages, or alternative dosing schedules. Significant effects on longevity, in one or both sexes, have been documented and then confirmed for NDGA, rapamycin, acarbose, and 17-a-estradiol (17aE2), with significant (but currently unconfirmed) effects also noted for Protandim, glycine and, in an interim analysis, canagliflozin. Lifespan trials are now underway for 18 new agents. ITP survival results have also documented longevity benefits from three agents started in middle-age: rapamycin, acarbose, and 17aE2. The previous five year period has introduced three new features to the ITP: increased emphasis on health outcomes (functional tests relevant to human health not necessarily linked to lifespan), a Collaborative Interactions Program to provide tissues from ITP drug-treated mice to an open, growing, international network of scientific collaborators, and a publicly accessible data repository and display engine hosted by the Mouse Phenome Database at the Jackson Laboratory. Plans for the next five-year period include additional lifespan (\Stage I\) trials, detailed analyses (\Stage II\) of agents found to increase lifespan, continued growth in data on health outcomes, and collaborative work with scientists to study drug effects on postulated aging mechanisms and links to disease. Studies at Michigan will follow up our analyses of cellular pathways relevant to stress resistance and inflammation, by continuing ongoing studies of cap-independent protein translation, chaperone mediated autophagy, and browning of white adipose cells. The work proposed should allow the ITP to continue to make major contributions to mammalian aging biology.
27. Project Title: ASPirin in Reducing Events in the Elderly - eXTension
    NIH U19AG062682 / ( 2019 - 2024 )
  OVERALL RESEARCH PLAN - ABSTRACT / SUMMARY In the U.S., low dose aspirin (LDA) is one of the most widely used medications given its established role in the secondary prevention of cardiovascular disease (CVD). In recent years, several expert bodies, including the U.S. Preventive Services Task Force (USPSTF), have recommended the routine use of LDA for the primary prevention of both CVD and colorectal cancer (CRC) based on substantial data from prior randomized controlled trials (RCTs) primarily conducted among younger adults. However, for adults aged 70+, the USPSTF deemed current evidence supporting a net benefit insufficient. Furthermore, the need to prolong healthy independent life, free of dementia and significant disability, is critical given the rising social and economic costs of the increasingly aging population. To address these knowledge gaps, the NIA/NCI- sponsored ASPirin in Reducing Events in the Elderly (ASPREE) study was developed as a ground-breaking RCT that recruited 19,114 initially healthy older individuals aged 70+ years (65+ for U.S. minorities) from 2010- 2014 in the U.S. and Australia to examine whether initiation of 5 years of low-dose daily aspirin (LDA; 100 mg/day) prolonged the healthy lifespan of older adults. In June 2017, the randomized treatment phase of ASPREE was suspended after a median of 4.6 years of treatment due to lack of an effect of LDA on the primary outcome of disability-free survival (DFS). For secondary outcomes, LDA unexpectedly was associated with an increased risk of all-cause mortality (HR 1.14; 95% CI, 1.01,1.28) driven by an excess of deaths due to cancer, despite no increase in incident cancer. Furthermore, LDA showed a trend toward lower incident physical disability overall. These provocative initial findings obligate continued study and follow-up of the ASPREE cohort through this U19 proposal. Our overall goal is to generate fundamental knowledge about the role of aspirin in older adults, a population in which aspirin's risk/benefit for primary prevention of chronic disease has been understudied. Our overarching hypothesis is that extended follow-up of the ASPREE cohort will demonstrate a long-term `legacy' benefit of LDA on cancer, dementia and disability. We further hypothesize that extensive genomic, biochemical, and imaging correlates collected during follow-up will offer unique biological insight into LDA's effects on these endpoints that may lead to mechanistically-inspired biomarkers for more `precision' prevention approaches to chronic disease prevention. Thus, we propose to establish ASPREE-XT to extend follow-up in ASPREE participants over the next 5 years to pursue three Projects focused on cancer, dementia (including Alzheimer's), and physical disability that will be supported by 6 Cores, facilitating synergy and collaboration. Together, this U19, led by a multidisciplinary, international team of leading investigators, will provide an unprecedented opportunity to define the long-term efficacy of LDA to guide clinical recommendations and offer fundamental insights into the biological underpinnings of the leading causes of dementia, disability and death among older adults.
28. Project Title: Janssen COVID-19 Vaccine Trial (\Ensemble\): A Randomized, Double-blind, Placebo-controlled Phase 3 Study to Assess the Efficacy and Safety of Ad26.COV2.S for the Prevention of SARS-CoV-2-mediated COVID-19 in Adults Aged 18 Years and Older
  Leader(s): LUGOGO, NJIRA
    JANSSEN VACCINES AND PREVENTION BV VAC31518COV3001 / ( 2020 - 2023 )
  University of Michigan is a site for this clinical trial and 147 subjects are anticipated to engage in the revised Month 6 Visit. A Randomized, Double-blind, Placebo-controlled Phase 3 Study to Assess the Efficacy and Safety of Ad26.COV2.S for the Prevention of SARS-CoV-2-mediated COVID-19 in Adults Aged 18 Years and Older. This study is being conducted under the sponsorship of Janssen (Janssen Vaccines & Prevention B.V) in collaboration with Operation Warp Speed (OWS), which also encompasses the Biomedical Advanced Research and Development Authority (BARDA), the National Institutes of Health (NIH), and the COVID-19 Prevention Trials Network (COVPN). Ad26.COV2.S (previously known as Ad26COVS1) is a monovalent vaccine composed of a recombinant, replication-incompetent adenovirus type 26 (Ad26) vector, constructed to encode the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike (S) protein. Information about the disease, correlates of immunity, and safety issues concerning this new pandemic-causing virus are rapidly evolving. Therefore, it is critical to recognize that the approach outlined in this document might or will change as insights and discussions evolve.
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    Citations: 1 | AltScore: 9
  12. Canagliflozin Increases Intestinal Adenoma Burden in Female ApcMin/+ Mice.
    Korfhage J, Skinner ME, Basu J, Greenson JK, Miller RA, Lombard DB
    J Gerontol A Biol Sci Med Sci, 2022 Feb 3, 77(2): 215-220 | PMID: 34448851 | PMCID: PMC8824675
    Citations: 1 | AltScore: 12.25
  13. Neutrophil and natural killer cell imbalances prevent muscle stem cell-mediated regeneration following murine volumetric muscle loss.
    Larouche JA, Fraczek PM, Kurpiers SJ, Yang BA, Davis C, Castor-Macias JA, Sabin K, Anderson S, Harrer J, Hall M, Brooks SV, Jang YC, Willett N, Shea LD, Aguilar CA
    Proc Natl Acad Sci U S A, 2022 Apr 12, 119(15): e2111445119 | PMID: 35377804 | PMCID: PMC9169656
    Citations: | AltScore: 95.45
  14. Provider Specialty and the Use of Disease-Modifying Antirheumatic Drugs for Rheumatoid Arthritis Among Older Adults in the 2005-2016 National Ambulatory Medical Care Survey.
    Lee J, Chang CH, Yung R, Bynum JPW
    ACR Open Rheumatol, 2022 Jan 17, 4(4): 332-337 | PMID: 35040280 | PMCID: PMC8992459
    Citations: | AltScore: 153.43
  15. Modeling success: How to work effectively with your biostatistician.
    Lee J, Kamdar BB, Bergstrom J, Murphy TE, Gill TM
    J Am Geriatr Soc, 2022 May 24 | PMID: 35608207
    Citations: | AltScore: 31.95
  16. Association Between Informant-Reported Sleep Disturbance and Incident Dementia: An Analysis of the National Alzheimer's Coordinating Center Uniform Data Set.
    Lee W, Gray SL, Barthold D, Maust DT, Marcum ZA
    J Appl Gerontol, 2022 Jan, 41(1): 285-294 | PMID: 33095080 | PMCID: PMC8062578
    Citations: 2 | AltScore: 10.25
  17. Disparities in Health Care Task Participation and Provider Communication by Family Caregiver Race.
    Leggett AN, Strominger J, Robinson-Lane SG, Maust DT
    J Gen Intern Med, 2022 Apr, 37(5): 1321-1324 | PMID: 33830417 | PMCID: PMC8971267
    Citations: | AltScore: 4.35
  18. Opioid and CNS-Depressant Medication Prescribing among Older Adults Enrolled in Medicare Advantage Versus Fee-for-Service Medicare.
    Lei L, Bynum JP, Maust DT
    Am J Geriatr Psychiatry, 2022 Feb, 30(2): 249-255 | PMID: 34565660 | PMCID: PMC8810693
    Citations: 1 | AltScore: NA
  19. Delayed Care Related to COVID-19 in a Nationally Representative Sample of Older Americans.
    Lei L, Maust DT
    J Gen Intern Med, 2022 Apr, 37(5): 1337-1340 | PMID: 35102478 | PMCID: PMC8802741
    Citations: | AltScore: 8.05
  20. Transient early life growth hormone exposure permanently alters brain, muscle, liver, macrophage, and adipocyte status?in long-lived Ames dwarf mice.
    Li X, McPherson M, Hager M, Fang Y, Bartke A, Miller RA
    FASEB J, 2022 Jul, 36(7): e22394 | PMID: 35704312 | PMCID: PMC9250136
    Citations: | AltScore: NA
  21. Paclitaxel mitigates structural alterations and cardiac conduction system defects in a mouse model of Hutchinson-Gilford progeria syndrome.
    Mac?as ?, D?az-Larrosa JJ, Blanco Y, Fanjul V, Gonz?lez-G?mez C, Gonzalo P, Andr?s-Manzano MJ, da Rocha AM, Ponce-Balbuena D, Allan A, Filgueiras-Rama D, Jalife J, Andr?s V
    Cardiovasc Res, 2022 Jan 29, 118(2): 503-516 | PMID: 33624748 | PMCID: PMC8803078
    Citations: 3 | AltScore: 3.35
  22. Racial Differences in Trust and Risk Disclosure Preferences Among Older Registered Research Volunteers Screened for Prodromal Synucleinopathies.
    Marshall C, Havis I, Herreshoff E, Lewis C, Kotagal V
    Gerontol Geriatr Med, 2022 Jan-Dec, 8: 23337214221094184 | PMID: 35601119 | PMCID: PMC9121461
    Citations: | AltScore: 9.5
  23. Environmental contamination with SARS-CoV-2 in nursing homes.
    Mody L, Gibson KE, Mantey J, Bautista L, Montoya A, Neeb K, Jenq G, Mills JP, Min L, Kabeto M, Galecki A, Cassone M, Martin ET
    J Am Geriatr Soc, 2022 Jan, 70(1): 29-39 | PMID: 34674220 | PMCID: PMC8661527
    Citations: 2 | AltScore: 334.999999999999
  24. Clin-Star corner: A new series featuring practice-changing articles in medical, surgical, and related specialties.
    Mody L, Gill TM, Zieman SJ
    J Am Geriatr Soc, 2022 Jun 15 | PMID: 35704905
    Citations: | AltScore: 14.45
  25. Gender Differences in Work-Family Conflict Experiences of Faculty in Academic Medicine.
    Mody L, Griffith KA, Jones RD, Stewart A, Ubel PA, Jagsi R
    J Gen Intern Med, 2022 Jan, 37(1): 280-282 | PMID: 33469767 | PMCID: PMC8739409
    Citations: 3 | AltScore: 4.1
  26. Metabolic Syndrome Trajectories and Objective Physical Performance in Mid-to-Early Late Life: The Study of Women's Health Across the Nation (SWAN).
    Napoleone JM, Boudreau RM, Lange-Maia BS, El Khoudary SR, Ylitalo KR, Kriska AM, Karvonen-Gutierrez CA, Strotmeyer ES
    J Gerontol A Biol Sci Med Sci, 2022 Feb 3, 77(2): e39-e47 | PMID: 34216218 | PMCID: PMC8824556
    Citations: 1 | AltScore: 8.75
  27. Prognostic Value of a Polygenic Risk Score for Coronary Heart Disease in Individuals Aged 70 Years and Older.
    Neumann JT, Riaz M, Bakshi A, Polekhina G, Thao LTP, Nelson MR, Woods RL, Abraham G, Inouye M, Reid CM, Tonkin AM, McNeil J, Lacaze P
    Circ Genom Precis Med, 2022 Feb, 15(1): e003429 | PMID: 34949098 | PMCID: PMC8847323
    Citations: 1 | AltScore: 17.6
  28. A multistate model of health transitions in older people: a secondary analysis of ASPREE clinical trial data.
    Neumann JT, Thao LTP, Callander E, Carr PR, Qaderi V, Nelson MR, Reid CM, Woods RL, Orchard SG, Wolfe R, Polekhina G, Williamson JD, Trauer JM, Newman AB, Murray AM, Ernst ME, Tonkin AM, McNeil JJ
    Lancet Healthy Longev, 2022 Feb, 3(2): e89-e97 | PMID: 35224525 | PMCID: PMC8880962
    Citations: | AltScore: NA
  29. Host-microbe interactions and outcomes in multiple myeloma and hematopoietic stem cell transplantation.
    Pianko MJ, Golob JL
    Cancer Metastasis Rev, 2022 Apr 29 | PMID: 35488106
    Citations: | AltScore: 8.9
  30. Caregiver status and illness self-efficacy during the COVID-19 pandemic among older adults with chronic conditions.
    Polenick CA, Lei L, Zhou AN, Birditt KS, Maust DT
    Aging Ment Health, 2022 Mar, 26(3): 563-569 | PMID: 33749447 | PMCID: PMC8455715
    Citations: 1 | AltScore: 11.45
  31. Bad company: Loneliness longitudinally predicts the symptom cluster of pain, fatigue, and depression in older adults.
    Powell VD, Kumar N, Galecki AT, Kabeto M, Clauw DJ, Williams DA, Hassett A, Silveira MJ
    J Am Geriatr Soc, 2022 Apr 12 | PMID: 35415848
    Citations: | AltScore: 21.35
  32. Aging is associated with increased brain iron through cortex-derived hepcidin expression.
    Sato T, Shapiro JS, Chang HC, Miller RA, Ardehali H
    Elife, 2022 Jan 11, 11:
    pii: e73456. | PMID: 35014607 | PMCID: PMC8752087
    Citations: 2 | AltScore: 73.73
  33. Mechanisms of pelvic floor muscle training for managing urinary incontinence in women: a scoping review.
    Sheng Y, Carpenter JS, Ashton-Miller JA, Miller JM
    BMC Womens Health, 2022 May 13, 22(1): 161 | PMID: 35562699 | PMCID: PMC9103460
    Citations: | AltScore: 1
  34. Regulation of mTOR complexes in long-lived growth hormone receptor knockout and Snell dwarf mice.
    Shi X, Endicott SJ, Miller RA
    Aging (Albany NY), 2022 Mar 19, 14(6): 2442-2461 | PMID: 35305083 | PMCID: PMC9004569
    Citations: 1 | AltScore: 7.2
  35. Factors Associated With 10-Year Declines in Physical Health and Function Among Women During Midlife.
    Solomon DH, Colvin A, Lange-Maia BS, Derby C, Dugan S, Jackson EA, Ruppert K, Karvonen-Gutierrez C, Santacroce L, Strotmeyer ES, Avis NE
    JAMA Netw Open, 2022 Jan 4, 5(1): e2142773 | PMID: 35006247 | PMCID: PMC8749479
    Citations: | AltScore: 933.104
  36. Functional and Cognitive Decline Among Older Adults After High-risk Surgery.
    Suwanabol PA, Li Y, Abrahamse P, De Roo AC, Vu JV, Silveira MJ, Mody L, Dimick JB
    Ann Surg, 2022 Jan 1, 275(1): e132-e139 | PMID: 32404660 | PMCID: PMC8060894
    Citations: | AltScore: 8.2
  37. Pelvic floor muscle injury during a difficult labor. Can tissue fatigue damage play a role?
    Vila Pouca MCP, Parente MPL, Natal Jorge RM, DeLancey JOL, Ashton-Miller JA
    Int Urogynecol J, 2022 Feb, 33(2): 211-220 | PMID: 34783861 | PMCID: PMC8959084
    Citations: 2 | AltScore: 2.85
  38. Rapamycin, Acarbose and 17a-estradiol share common mechanisms regulating the MAPK pathways involved in intracellular signaling and inflammation.
    Wink L, Miller RA, Garcia GG
    Immun Ageing, 2022 Feb 1, 19(1): 8 | PMID: 35105357 | PMCID: PMC8805398
    Citations: | AltScore: 6.1
  1. Team VA Video Connect (VVC) to optimize mobility and physical activity in post-hospital discharge older veterans: baseline assessment.
    Alexander NB, Phillips K, Wagner-Felkey J, Chan CL, Hogikyan R, Sciaky A, Cigolle C
    BMC Geriatr, 2021 Sep 22, 21(1): 502 | PMID: 34551725 | PMCID: PMC8456191
    Citations: | AltScore: 1
  2. On Structure-Function Relationships in the Female Human Urethra: A Finite Element Model Approach.
    Attari A, DeLancey JO, Ashton-Miller JA
    Ann Biomed Eng, 2021 Aug, 49(8): 1848-1860 | PMID: 33782810 | PMCID: PMC8376757
    Citations: | AltScore: 2.35
  3. Factors associated with antihypertensive treatment intensification and deintensification in older outpatients.
    Aubert CE, Ha JK, Kerr EA, Hofer TP, Min L
    Int J Cardiol Hypertens, 2021 Jun, 9: 100098 | PMID: 34258575 | PMCID: PMC8254109
    Citations: | AltScore: 4.1
  4. Clinical outcomes of modifying hypertension treatment intensity in older adults treated to low blood pressure.
    Aubert CE, Ha JK, Kim HM, Rodondi N, Kerr EA, Hofer TP, Min L
    J Am Geriatr Soc, 2021 Oct, 69(10): 2831-2841 | PMID: 34097300 | PMCID: PMC8497391
    Citations: 1 | AltScore: 14.4
  5. Adding a New Medication Versus Maximizing Dose to Intensify Hypertension Treatment in Older Adults : A Retrospective Observational Study.
    Aubert CE, Sussman JB, Hofer TP, Cushman WC, Ha JK, Min L
    Ann Intern Med, 2021 Dec, 174(12): 1666-1673 | PMID: 34606315 | PMCID: PMC9012609
    Citations: 1 | AltScore: 261.26
  6. Dual trajectories of physical activity and blood lipids in midlife women: The Study of Women's Health Across the Nation.
    Badon SE, Gabriel KP, Karvonen-Gutierrez C, Sternfeld B, Gold EB, Waetjen LE, Lee C, Avalos LA, El Khoudary SR, Hedderson MM
    Maturitas, 2021 Apr, 146: 49-56 | PMID: 33722364 | PMCID: PMC7966732
    Citations: 1 | AltScore: NA
  7. A Polygenic Risk Score Predicts Incident Prostate Cancer Risk in Older Men but Does Not Select for Clinically Significant Disease.
    Bakshi A, Riaz M, Orchard SG, Carr PR, Joshi AD, Cao Y, Rebello R, Nguyen-Dumont T, Southey MC, Millar JL, Gately L, Gibbs P, Ford LG, Parnes HL, Chan AT, McNeil JJ, Lacaze P
    Cancers (Basel), 2021 Nov 19, 13(22):
    pii: 5815. | PMID: 34830967 | PMCID: PMC8616400
    Citations: 1 | AltScore: 2.25
  8. Cumulative Genetic Risk and APOE e4 Are Independently Associated With Dementia Status in a Multiethnic, Population-Based Cohort.
    Bakulski KM, Vadari HS, Faul JD, Heeringa SG, Kardia SLR, Langa KM, Smith JA, Manly JJ, Mitchell CM, Benke KS, Ware EB
    Neurol Genet, 2021 Apr, 7(2): e576 | PMID: 33688582 | PMCID: PMC7938646
    Citations: 1 | AltScore: 26.1
  9. Does it Matter Who Decides? Outcomes of Surrogate Decision-Making for Community-Dwelling, Cognitively Impaired Older Adults Near the End of Life.
    Baum MY, Gallo JJ, Nolan MT, Langa KM, Halpern SD, Macis M, Nicholas LH
    J Pain Symptom Manage, 2021 Dec, 62(6): 1126-1134 | PMID: 34153462 | PMCID: PMC8648882
    Citations: | AltScore: NA
  10. Effects of aspirin on the long-term management of depression in older people: a double-blind randomised placebo-controlled trial.
    Berk M, Agustini B, Woods RL, Nelson MR, Shah RC, Reid CM, Storey E, Fitzgerald SM, Lockery JE, Wolfe R, Mohebbi M, Dodd S, Murray AM, Stocks N, Fitzgerald PB, Mazza C, McNeil JJ
    Mol Psychiatry, 2021 Sep, 26(9): 5161-5170 | PMID: 33504953 | PMCID: PMC8313623
    Citations: 2 | AltScore: 2.5
  11. The Influence of Cognitive Impairment on Post-Operative Outcomes.
    Blair EM, Levine DA, Hu HM, Langa KM, Kabeto MU, Waljee J
    Ann Surg, 2021 Feb 10 | PMID: 33605584 | PMCID: PMC8353015
    Citations: | AltScore: 3.5
  12. Metabolic syndrome and the benefit of a physical activity intervention on lower-extremity function: Results from a randomized clinical trial.
    Botoseneanu A, Chen H, Ambrosius WT, Allore HG, Anton S, Folta SC, King AC, Nicklas BJ, Spring B, Strotmeyer ES, Gill TM
    Exp Gerontol, 2021 Jul 15, 150: 111343 | PMID: 33848565 | PMCID: PMC8388825
    Citations: 2 | AltScore: 5.45
  13. Pre-Statistical Considerations for Harmonization of Cognitive Instruments: Harmonization of ARIC, CARDIA, CHS, FHS, MESA, and NOMAS.
    Brice?o EM, Gross AL, Giordani BJ, Manly JJ, Gottesman RF, Elkind MSV, Sidney S, Hingtgen S, Sacco RL, Wright CB, Fitzpatrick A, Fohner AE, Mosley TH, Yaffe K, Levine DA
    J Alzheimers Dis, 2021, 83(4): 1803-1813 | PMID: 34459397 | PMCID: PMC8733857
    Citations: | AltScore: 13.65
  14. Bilingualism, assessment language, and the Montreal Cognitive Assessment in Mexican Americans.
    Brice?o EM, Mehdipanah R, Gonzales XF, Heeringa SG, Levine DA, Langa KM, Zahs D, Garcia N, Longoria R, Morgenstern LB
    J Am Geriatr Soc, 2021 Jul, 69(7): 1971-1981 | PMID: 33963535 | PMCID: PMC8273138
    Citations: | AltScore: 16.15
  15. Differential Relationships Between the Montreal Cognitive Assessment and Informant-Rated Cognitive Decline Among Mexican Americans and Non-Hispanic Whites.
    Brice?o EM, Mehdipanah R, Gonzales XF, Heeringa SG, Levine DA, Langa KM, Zahs D, Garcia N, Longoria R, Vargas A, Morgenstern LB
    J Geriatr Psychiatry Neurol, 2021 Jul 22, 35(4): 555-564 | PMID: 34291678 | PMCID: PMC8782915
    Citations: | AltScore: 12.35
  16. Not too close! impact of roommate status on MRSA and VRE colonization and contamination in Nursing Homes.
    Cassone M, Linder M, Shin CJ, Mantey J, Gibson K, Lansing B, Mody L
    Antimicrob Resist Infect Control, 2021 Jul 5, 10(1): 104 | PMID: 34225783 | PMCID: PMC8258944
    Citations: | AltScore: 5.25
  17. Seasonal Patterns in Incidence and Antimicrobial Resistance of Common Bacterial Pathogens in Nursing Home Patients and Their Rooms.
    Cassone M, Mantey J, Gontjes KJ, Lansing BJ, Gibson KE, Wang J, Mody L
    Front Public Health, 2021, 9: 671428 | PMID: 34322470 | PMCID: PMC8311345
    Citations: | AltScore: 4.25
  18. Measuring the outsized impact of COVID-19 in the evolving setting of aged care facilities.
    Cassone M, Mody L
    EClinicalMedicine, 2021 Apr, 34: 100825 | PMID: 33880439 | PMCID: PMC8050616
    Citations: 1 | AltScore: 1.5
  19. Microscopic examination of spatial transcriptome using Seq-Scope.
    Cho CS, Xi J, Si Y, Park SR, Hsu JE, Kim M, Jun G, Kang HM, Lee JH
    Cell, 2021 Jun 24, 184(13): 3559-3572.e22 | PMID: 34115981 | PMCID: PMC8238917
    Citations: 8 | AltScore: 191.746
  20. Family Care Availability And Implications For Informal And Formal Care Used By Adults With Dementia In The US.
    Choi H, Heisler M, Norton EC, Langa KM, Cho TC, Connell CM
    Health Aff (Millwood), 2021 Sep, 40(9): 1359-1367 | PMID: 34495713 | PMCID: PMC8647567
    Citations: | AltScore: 131.03
  21. Perfluoroalkyl and polyfluoroalkyl substances and body size and composition trajectories in midlife women: the study of women's health across the nation 1999-2018.
    Ding N, Karvonen-Gutierrez CA, Herman WH, Calafat AM, Mukherjee B, Park SK
    Int J Obes (Lond), 2021 Sep, 45(9): 1937-1948 | PMID: 33986457 | PMCID: PMC8384652
    Citations: 4 | AltScore: 10.35
  22. Associations of perfluoroalkyl and polyfluoroalkyl substances (PFAS) and PFAS mixtures with adipokines in midlife women.
    Ding N, Karvonen-Gutierrez CA, Herman WH, Calafat AM, Mukherjee B, Park SK
    Int J Hyg Environ Health, 2021 Jun, 235: 113777 | PMID: 34090141 | PMCID: PMC8207532
    Citations: 2 | AltScore: 1
  23. The Longitudinal Association of Vision Impairment With Transitions to Cognitive Impairment and Dementia: Findings From the Aging, Demographics and Memory Study.
    Ehrlich JR, Swenor BK, Zhou Y, Langa KM
    J Gerontol A Biol Sci Med Sci, 2021 Nov 15, 76(12): 2187-2193 | PMID: 34061956 | PMCID: PMC8599065
    Citations: 1 | AltScore: 4.5
  24. Effect of aspirin on deaths associated with sepsis in healthy older people (ANTISEPSIS): a randomised, double-blind, placebo-controlled primary prevention trial.
    Eisen DP, Leder K, Woods RL, Lockery JE, McGuinness SL, Wolfe R, Pilcher D, Moore EM, Shastry A, Nelson MR, Reid CM, McNeil JJ, McBryde ES
    Lancet Respir Med, 2021 Feb, 9(2): 186-195 | PMID: 32950072 | PMCID: PMC7957956
    Citations: 14 | AltScore: 32.4
  25. Long-lived mice with reduced growth hormone signaling have a constitutive upregulation of hepatic chaperone-mediated autophagy.
    Endicott SJ, Boynton DN Jr, Beckmann LJ, Miller RA
    Autophagy, 2021 Mar, 17(3): 612-625 | PMID: 32013718 | PMCID: PMC8032237
    Citations: 7 | AltScore: 0.75
  26. Long-Term Blood Pressure Variability and Risk of Cognitive Decline and Dementia Among Older Adults.
    Ernst ME, Ryan J, Chowdhury EK, Margolis KL, Beilin LJ, Reid CM, Nelson MR, Woods RL, Shah RC, Orchard SG, Wolfe R, Storey E, Tonkin AM, Brodtmann A, McNeil JJ, Murray AM
    J Am Heart Assoc, 2021 Jul 6, 10(13): e019613 | PMID: 34176293 | PMCID: PMC8403315
    Citations: 5 | AltScore: 808.4
  27. The Effect of Childhood Socioeconomic Position and Social Mobility on Cognitive Function and Change Among Older Adults: A Comparison Between the United States and England.
    Faul JD, Ware EB, Kabeto MU, Fisher J, Langa KM
    J Gerontol B Psychol Sci Soc Sci, 2021 Jun 8, 76(Suppl 1): S51-S63 | PMID: 34101811 | PMCID: PMC8186857
    Citations: 1 | AltScore: 123.05
  28. Relationship between adult and family supporter health literacy levels and supporter roles in diabetes management.
    Fields B, Lee A, Piette JD, Trivedi R, Mor MK, Obrosky DS, Heisler M, Rosland AM
    Fam Syst Health, 2021 Jun, 39(2): 224-233 | PMID: 33370140 | PMCID: PMC8717858
    Citations: | AltScore: 0.25
  29. Changes in medication use among long-stay residents with dementia in Michigan during the pandemic.
    Gerlach LB, Park PS, Shireman TI, Bynum JPW
    J Am Geriatr Soc, 2021 Apr 8, 69(7): 1743-1745 | PMID: 33834488 | PMCID: PMC8251218
    Citations: 1 | AltScore: 11.35
  30. The Most Common Medications Billed to the Medicare Hospice Benefit Among Hospice Beneficiaries in the U.S.
    Gerlach LB, Powell V, Zhang L, Bynum JPW, Maust DT
    J Pain Symptom Manage, 2021 Sep, 62(3): e3-e6 | PMID: 34051294 | PMCID: PMC8419064
    Citations: | AltScore: NA
  31. The COVID-19 Pandemic and Mental Health Symptoms Among US Adults.
    Gerlach LB, Solway E, Maust DT, Kirch M, Kullgren JT, Singer DC, Malani PN
    J Gen Intern Med, 2021 Oct, 36(10): 3285-3288 | PMID: 34318381 | PMCID: PMC8315247
    Citations: 3 | AltScore: 139.3
  32. Evaluation of the Pain Impact Index for Community-Dwelling Older Adults Through the Application of Rasch Modelling.
    Gilmartin-Thomas JF, Forbes A, Liew D, McNeil JJ, Cicuttini FM, Owen AJ, Ernst ME, Nelson MR, Lockery J, Ward SA, Busija L, ASPREE Investigator Group.
    Pain Pract, 2021 Jun, 21(5): 501-512 | PMID: 33295122 | PMCID: PMC8187294
    Citations: | AltScore: 7.58
  33. Can alternative anatomical sites and environmental surveillance replace perianal screening for multidrug-resistant organisms in nursing homes?
    Gontjes KJ, Gibson KE, Lansing B, Cassone M, Mody L
    Infect Control Hosp Epidemiol, 2021 May 21 1-4 | PMID: 34016196 | PMCID: PMC9190292
    Citations: 1 | AltScore: 4.7
  34. Longitudinal Assessment of Physical Activity and Cognitive Outcomes Among Women at Midlife.
    Greendale GA, Han W, Huang M, Upchurch DM, Karvonen-Gutierrez C, Avis NE, Karlamangla AS
    JAMA Netw Open, 2021 Mar 1, 4(3): e213227 | PMID: 33787912 | PMCID: PMC8013795
    Citations: 2 | AltScore: 76.78
  35. Increase in C-Reactive Protein Predicts Increase in Rate of Bone Mineral Density Loss: The Study of Women's Health Across the Nation.
    Greendale GA, Jackson NJ, Han W, Huang M, Cauley JA, Karvonen-Gutierrez C, Karlamangla AS
    JBMR Plus, 2021 Apr, 5(4): e10480 | PMID: 33869996 | PMCID: PMC8046126
    Citations: 1 | AltScore: 2.25
  36. 17-a-estradiol late in life extends lifespan in aging UM-HET3 male mice; nicotinamide riboside and three other drugs do not affect lifespan in either sex.
    Harrison DE, Strong R, Reifsnyder P, Kumar N, Fernandez E, Flurkey K, Javors MA, Lopez-Cruzan M, Macchiarini F, Nelson JF, Bitto A, Sindler AL, Cortopassi G, Kavanagh K, Leng L, Bucala R, Rosenthal N, Salmon A, Stearns TM, Bogue M, Miller RA
    Aging Cell, 2021 May, 20(5): e13328 | PMID: 33788371 | PMCID: PMC8135004
    Citations: 6 | AltScore: 70.438
  37. Automated Loss-of-Balance Event Identification in Older Adults at Risk of Falls during Real-World Walking Using Wearable Inertial Measurement Units.
    Hauth J, Jabri S, Kamran F, Feleke EW, Nigusie K, Ojeda LV, Handelzalts S, Nyquist L, Alexander NB, Huan X, Wiens J, Sienko KH
    Sensors (Basel), 2021 Jul 7, 21(14):
    pii: 4661. | PMID: 34300399 | PMCID: PMC8309544
    Citations: 1 | AltScore: NA
  38. Investigating Racial Differences among Men in COVID-19 Diagnosis, and Related Psychosocial and Behavioral Factors: Data from the Michigan Men's Health Event.
    Hawkins J, Gilcher K, Schwenzer C, Lutz M
    Int J Environ Res Public Health, 2021 Mar 22, 18(6):
    pii: 3284. | PMID: 33810055 | PMCID: PMC8005096
    Citations: | AltScore: 17
  39. Michigan Men's diabetes project (MenD): protocol for a peer leader diabetes self-management education and support intervention.
    Hawkins J, Kloss K, Funnell M, Nwankwo R, Schwenzer C, Smith F, Piatt G
    BMC Public Health, 2021 Mar 22, 21(1): 562 | PMID: 33752609 | PMCID: PMC7983198
    Citations: | AltScore: 8
  40. Skeletal muscle RBM3 expression is associated with extended lifespan in Ames Dwarf and calorie restricted mice.
    Hettinger ZR, Confides AL, Vanderklish PW, Sidhom S, Masternak MM, Dupont-Versteegden EE
    Exp Gerontol, 2021 Apr, 146: 111214 | PMID: 33385482 | PMCID: PMC7902444
    Citations: 1 | AltScore: 4.1
  41. Alzheimer's Disease and Related Dementias and Episode Spending Under Medicare's Bundled Payment for Care Improvements Advanced (BPCI-A).
    Hoffman GJ, Nuliyalu U, Bynum J, Ryan AM
    J Gen Intern Med, 2021 Aug, 36(8): 2499-2502 | PMID: 33236227 | PMCID: PMC8342721
    Citations: | AltScore: 2
  42. Flavin-Containing Monooxygenases Are Conserved Regulators of Stress Resistance and Metabolism.
    Huang S, Howington MB, Dobry CJ, Evans CR, Leiser SF
    Front Cell Dev Biol, 2021, 9: 630188 | PMID: 33644069 | PMCID: PMC7907451
    Citations: 4 | AltScore: 2
  43. A New Panel-Estimated GFR, Including ?2-Microglobulin and ?-Trace Protein and Not Including Race, Developed in a Diverse Population.
    Inker LA, Couture SJ, Tighiouart H, Abraham AG, Beck GJ, Feldman HI, Greene T, Gudnason V, Karger AB, Eckfeldt JH, Kasiske BL, Mauer M, Navis G, Poggio ED, Rossing P, Shlipak MG, Levey AS, CKD-EPI GFR Collaborators.
    Am J Kidney Dis, 2021 May, 77(5): 673-683.e1 | PMID: 33301877 | PMCID: PMC8102017
    Citations: 9 | AltScore: 176.76
  44. When planning meets reality: COVID-19 interpandemic survey of Michigan Nursing Homes.
    Jones K, Mantey J, Washer L, Meddings J, Patel PK, Montoya A, Mills JP, Gibson K, Mody L
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  54. Diabetes Distress Among Dyads of Patients and Their Health Supporters: Links With Functional Support, Metabolic Outcomes, and Cardiac Risk.
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    Ann Behav Med, 2021 Oct 4, 55(10): 949-955 | PMID: 33044495 | PMCID: PMC8677591
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  55. Medicare beneficiary panel characteristics associated with high Part D biologic disease-modifying anti-rheumatic drug prescribing for older adults among rheumatologists.
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  56. Urinary concentrations of phenols and parabens and incident diabetes in midlife women: The Study of Women's Health Across the Nation.
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    Environ Epidemiol, 2021 Oct, 5(5): e171 | PMID: 34934892 | PMCID: PMC8683147
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  57. Benzodiazepine Prescribing from VA and Medicare to Dually Enrolled Older Veterans: A Retrospective Cohort Study.
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  58. Preexisting Mild Cognitive Impairment, Dementia, and Receipt of Treatments for Acute Ischemic Stroke.
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  59. Sex Differences in Cognitive Decline Among US Adults.
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  60. Identification of Trigeminal Sensory Neuronal Types Innervating Masseter Muscle.
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  61. Same-Sex Couples and Cognitive Impairment: Evidence From the Health and Retirement Study.
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  62. A Cohort Study of Anticholinergic Medication Burden and Incident Dementia and Stroke in Older Adults.
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  63. A TORC1-histone axis regulates chromatin organisation and non-canonical induction of autophagy to ameliorate ageing.
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  64. Targeted gown and glove use to prevent Staphylococcus aureus acquisition in community-based nursing homes: A pilot study.
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  65. Major GI bleeding in older persons using aspirin: incidence and risk factors in the ASPREE randomised controlled trial.
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  66. Metabolipidomic profiling reveals an age-related deficiency of skeletal muscle pro-resolving mediators that contributes to maladaptive tissue remodeling.
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  67. Identifying Cohabiting Couples in Administrative Data: Evidence from Medicare Address Data.
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  68. Prevalence of Central Nervous System-Active Polypharmacy Among Older Adults With Dementia in the US.
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  69. Effect of Aspirin on Cancer Incidence and Mortality in Older Adults.
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    J Natl Cancer Inst, 2021 Mar 1, 113(3): 258-265 | PMID: 32778876 | PMCID: PMC7936068
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  70. Dementia care needs for individuals and caregivers among Mexican Americans and non-Hispanic Whites.
    Mehdipanah R, Brice?o EM, Gonzales XF, Heeringa SG, Levine DA, Langa KM, Garcia N, Longoria R, Morgenstern LB
    Aging Ment Health, 2021 Jun 7, 26(8): 1630-1641 | PMID: 34096422 | PMCID: PMC8864934
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  71. Risk Factors for and Mechanisms of COlistin Resistance Among Enterobacterales: Getting at the CORE of the Issue.
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    Open Forum Infect Dis, 2021 Jul, 8(7): ofab145 | PMID: 34285928 | PMCID: PMC8286092
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  72. A Method to Quantify Mean Hypertension Treatment Daily Dose Intensity Using Health Care System Data.
    Min L, Ha JK, Aubert CE, Hofer TP, Sussman JB, Langa KM, Tinetti M, Kim HM, Maciejewski ML, Gillon L, Larkin A, Chan CL, Kerr EA, Bravata D, Cushman WC
    JAMA Netw Open, 2021 Jan 4, 4(1): e2034059 | PMID: 33449097 | PMCID: PMC7811181
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  73. Effectiveness of a Multicomponent Intervention to Reduce Multidrug-Resistant Organisms in Nursing Homes: A Cluster Randomized Clinical Trial.
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    JAMA Netw Open, 2021 Jul 1, 4(7): e2116555 | PMID: 34269807 | PMCID: PMC8285736
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  74. Short-, Medium-, and Long-term Weight Changes and All-Cause Mortality in Old Age: Findings From the National Survey of the Japanese Elderly.
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    J Gerontol A Biol Sci Med Sci, 2021 Oct 13, 76(11): 2039-2046 | PMID: 33626135 | PMCID: PMC8514062
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  75. Preparing nursing homes for a second wave of coronavirus disease 2019 (COVID-19).
    Murthy AR, Hanrahan JA, Advani SD, Ashraf MS, Mills JP, Mody L, Henderson DK, Hayden MK, Weber DJ, Wright SB, Babcock H, Guzman-Cottrill J, Haessler SD, Rock C, Van Schooneveld T, Forde C, Logan LK, Malani A
    Infect Control Hosp Epidemiol, 2021 Oct, 42(10): 1251-1254 | PMID: 33077005 | PMCID: PMC8458840
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  76. Association of Coding Variants in Hydroxysteroid 17-beta Dehydrogenase 14 (HSD17B14) with Reduced Progression to End Stage Kidney Disease in Type 1 Diabetes.
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  77. Predictive Performance of a Polygenic Risk Score for Incident Ischemic Stroke in a Healthy Older Population.
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    Stroke, 2021 Aug, 52(9): 2882-2891 | PMID: 34039031 | PMCID: PMC8384668
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  78. Financial Presentation of Alzheimer Disease and Related Dementias.
    Nicholas LH, Langa KM, Bynum JPW, Hsu JW
    JAMA Intern Med, 2021 Feb 1, 181(2): 220-227 | PMID: 33252621 | PMCID: PMC7851732
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  79. Behaviours of older adults and caregivers preparing for elective surgery: a virtually conducted mixed-methods research protocol to improve surgical outcomes.
    Norcott A, Chan CL, Nyquist L, Bynum JP, Min L, Fetters MD, DeJonckheere M
    BMJ Open, 2021 Oct 18, 11(10): e048299 | PMID: 34663655 | PMCID: PMC8524274
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  80. Preoperative Cognitive Evaluations: An Opportunity to Protect the Vulnerable Brain.
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    Ann Surg, 2021 Jul 1, 274(1): e85-e87 | PMID: 33156058
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  81. RNA-seq of human T cells after hematopoietic stem cell transplantation identifies Linc00402 as a regulator of T cell alloimmunity.
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  82. Muscle weakness is a prognostic indicator of disability and chronic disease multimorbidity.
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    Exp Gerontol, 2021 Sep, 152: 111462 | PMID: 34224846 | PMCID: PMC8462981
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  83. The Utility of Assessing Health-Related Quality of Life to Predict Cognitive Decline and Dementia.
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    J Alzheimers Dis, 2021, 80(2): 895-904 | PMID: 33579847 | PMCID: PMC8093030
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  84. Health-related quality of life and all-cause mortality among older healthy individuals in Australia and the United States: a prospective cohort study.
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    Qual Life Res, 2021 Apr, 30(4): 1037-1048 | PMID: 33389487 | PMCID: PMC8005489
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  85. Potential repurposing of the HDAC inhibitor valproic acid for patients with COVID-19.
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    Eur J Pharmacol, 2021 May 5, 898: 173988 | PMID: 33667455 | PMCID: PMC7923868
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  86. Unwelcome Companions: Loneliness Associates with the Cluster of Pain, Fatigue, and Depression in Older Adults.
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    Gerontol Geriatr Med, 2021 Jan-Dec, 7: 2333721421997620 | PMID: 33709010 | PMCID: PMC7907946
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  87. Symptom clusters predict risk of metabolic-syndrome and diabetes in midlife: the Study of Women's Health Across the Nation.
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    Ann Epidemiol, 2021 Jun, 58: 48-55 | PMID: 33631313 | PMCID: PMC8165007
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  88. Effect of APOE and a polygenic risk score on incident dementia and cognitive decline in a healthy older population.
    Riaz M, Huq A, Ryan J, Orchard SG, Tiller J, Lockery J, Woods RL, Wolfe R, Renton AE, Goate AM, Sebra R, Schadt E, Brodtmann A, Shah RC, Storey E, Murray AM, McNeil JJ, Lacaze P
    Aging Cell, 2021 Jun, 20(6): e13384 | PMID: 34041846 | PMCID: PMC8208779
    Citations: 3 | AltScore: 18.35
  89. Coping and adaptation to dementia family caregiving: A pilot study.
    Robinson-Lane SG, Zhang X, Patel A
    Geriatr Nurs, 2021 Jan-Feb, 42(1): 256-261 | PMID: 32891443 | PMCID: PMC7921211
    Citations: | AltScore: NA
  90. Gene-by-environment modulation of lifespan and weight gain in the murine BXD family.
    Roy S, Sleiman MB, Jha P, Ingels JF, Chapman CJ, McCarty MS, Ziebarth JD, Hook M, Sun A, Zhao W, Huang J, Neuner SM, Wilmott LA, Shapaker TM, Centeno AG, Ashbrook DG, Mulligan MK, Kaczorowski CC, Makowski L, Cui Y, Read RW, Miller RA, Mozhui K, Williams EG, Sen S, Lu L, Auwerx J, Williams RW
    Nat Metab, 2021 Sep, 3(9): 1217-1227 | PMID: 34552269 | PMCID: PMC8478125
    Citations: 3 | AltScore: 20.2
  91. CD4 receptor diversity represents an ancient protection mechanism against primate lentiviruses.
    Russell RM, Bibollet-Ruche F, Liu W, Sherrill-Mix S, Li Y, Connell J, Loy DE, Trimboli S, Smith AG, Avitto AN, Gondim MVP, Plenderleith LJ, Wetzel KS, Collman RG, Ayouba A, Esteban A, Peeters M, Kohler WJ, Miller RA, Fran?ois-Souquiere S, Switzer WM, Hirsch VM, Marx PA, Piel AK, Stewart FA, Georgiev AV, Sommer V, Bertolani P, Hart JA, Hart TB, Shaw GM, Sharp PM, Hahn BH
    Proc Natl Acad Sci U S A, 2021 Mar 30, 118(13):
    pii: e2025914118. | PMID: 33771926 | PMCID: PMC8020793
    Citations: 2 | AltScore: 13.2
  92. Subtle mistakes in self-report surveys predict future transition to dementia.
    Schneider S, Junghaenel DU, Zelinski EM, Meijer E, Stone AA, Langa KM, Kapteyn A
    Alzheimers Dement (Amst), 2021, 13(1): e12252 | PMID: 34934800 | PMCID: PMC8652408
    Citations: 1 | AltScore: 10
  93. Political affiliation and risk taking behaviors among adults with elevated chance of severe complications from COVID-19.
    Schoeni RF, Wiemers EE, Seltzer JA, Langa KM
    Prev Med, 2021 Dec, 153: 106726 | PMID: 34280407 | PMCID: PMC8284062
    Citations: | AltScore: 4.1
  94. Association Between Risk Factors for Complications From COVID-19, Perceived Chances of Infection and Complications, and Protective Behavior in the US.
    Schoeni RF, Wiemers EE, Seltzer JA, Langa KM
    JAMA Netw Open, 2021 Mar 1, 4(3): e213984 | PMID: 33787906 | PMCID: PMC8013830
    Citations: 4 | AltScore: 206.56
  95. Cap-independent translation: A shared mechanism for lifespan extension by rapamycin, acarbose, and 17a-estradiol.
    Shen Z, Hinson A, Miller RA, Garcia GG
    Aging Cell, 2021 May, 20(5): e13345 | PMID: 33742521 | PMCID: PMC8135077
    Citations: 5 | AltScore: 13.2
  96. Repeat RNA Toxicity Drives Ribosomal RNA Processing Defects in SCA2.
    Skariah G, Albin RL
    Mov Disord, 2021 Nov, 36(11): 2464-2467 | PMID: 34783387 | PMCID: PMC8604384
    Citations: | AltScore: 1
  97. Muribaculaceae Genomes Assembled from Metagenomes Suggest Genetic Drivers of Differential Response to Acarbose Treatment in Mice.
    Smith BJ, Miller RA, Schmidt TM
    mSphere, 2021 Dec 22, 6(6): e0085121 | PMID: 34851167 | PMCID: PMC8636109
    Citations: 5 | AltScore: 3
  98. Trends and Disparities in Functional Impairment among US Adults Age 55-64, 2002 to 2016.
    Tipirneni R, Karmakar M, Maust DT
    J Gen Intern Med, 2021 Dec, 36(12): 3903-3906 | PMID: 32918202 | PMCID: PMC8642514
    Citations: 1 | AltScore: NA
  99. Changes in Health Care Access and Utilization for Low-SES Adults Aged 51-64 Years After Medicaid Expansion.
    Tipirneni R, Levy HG, Langa KM, McCammon RJ, Zivin K, Luster J, Karmakar M, Ayanian JZ
    J Gerontol B Psychol Sci Soc Sci, 2021 Jun 14, 76(6): 1218-1230 | PMID: 32777052 | PMCID: PMC8200354
    Citations: 3 | AltScore: 16.5
  100. Age and Sex: Impact on adipose tissue metabolism and inflammation.
    Varghese M, Song J, Singer K
    Mech Ageing Dev, 2021 Oct, 199: 111563 | PMID: 34474078 | PMCID: PMC8490336
    Citations: 2 | AltScore: 1.5
  101. Fisetin for COVID-19 in skilled nursing facilities: Senolytic trials in the COVID era.
    Verdoorn BP, Evans TK, Hanson GJ, Zhu Y, Langhi Prata LGP, Pignolo RJ, Atkinson EJ, Wissler-Gerdes EO, Kuchel GA, Mannick JB, Kritchevsky SB, Khosla S, Rizza SA, Walston JD, Musi N, Lipsitz LA, Kiel DP, Yung R, LeBrasseur NK, Singh RJ, McCarthy T, Puskarich MA, Niedernhofer LJ, Robbins PD, Sorenson M, Tchkonia T, Kirkland JL
    J Am Geriatr Soc, 2021 Nov, 69(11): 3023-3033 | PMID: 34375437 | PMCID: PMC8447437
    Citations: 14 | AltScore: 27.708
  102. Injuries in Muscle-Tendon-Bone Units: A Systematic Review Considering the Role of Passive Tissue Fatigue.
    Vila Pouca MCP, Parente MPL, Jorge RMN, Ashton-Miller JA
    Orthop J Sports Med, 2021 Aug, 9(8): 23259671211020731 | PMID: 34395681 | PMCID: PMC8361535
    Citations: 2 | AltScore: NA
  103. Planning for Driving Retirement: The Effect of Driving Perceptions, Driving Events, and Assessment of Driving Alternatives.
    Vivoda JM, Cao J, Koumoutzis A, Harmon AC, Babulal GM
    Transp Res Part F Traffic Psychol Behav, 2021 Jan, 76: 193-201 | PMID: 33716551 | PMCID: PMC7945980
    Citations: 1 | AltScore: NA
  104. Urinary Heavy Metals and Longitudinal Changes in Blood Pressure in Midlife Women: The Study of Women's Health Across the Nation.
    Wang X, Karvonen-Gutierrez CA, Herman WH, Mukherjee B, Harlow SD, Park SK
    Hypertension, 2021 Aug, 78(2): 543-551 | PMID: 34148361 | PMCID: PMC8266752
    Citations: 1 | AltScore: 8.55
  105. Development, Validation, and Performance of a New Physical Functioning-Weighted Multimorbidity Index for Use in Administrative Data.
    Wei MY, Luster JE, Ratz D, Mukamal KJ, Langa KM
    J Gen Intern Med, 2021 Jan 19, 36(8): 2427-2433 | PMID: 33469748 | PMCID: PMC8342661
    Citations: 1 | AltScore: 1
  106. Subgroup analysis of the ASPirin in Reducing Events in the Elderly randomized clinical trial suggests aspirin did not improve outcomes in older adults with chronic kidney disease.
    Wolfe R, Wetmore JB, Woods RL, McNeil JJ, Gallagher H, Roderick P, Walker R, Nelson MR, Reid CM, Shah RC, Ernst ME, Lockery JE, Tonkin AM, Abhayaratna WP, Gibbs P, Wood EM, Mahady SE, Williamson JD, Donnan GA, Cloud GC, Murray AM, Polkinghorne KR
    Kidney Int, 2021 Feb, 99(2): 466-474 | PMID: 32920022 | PMCID: PMC7957958
    Citations: 3 | AltScore: 91.2
  107. Understanding short-term transmission dynamics of methicillin-resistant Staphylococcus aureus in the patient room.
    Wolfensberger A, Mang N, Gibson KE, Gontjes K, Cassone M, Brugger SD, Mody L, Sax H
    Infect Control Hosp Epidemiol, 2021 Aug 27 1-8 | PMID: 34448445 | PMCID: PMC9272746
    Citations: | AltScore: 0.25
  108. Exposure and risk factors for COVID-19 and the impact of staying home on Michigan residents.
    Wu KH, Hornsby WE, Klunder B, Krause A, Driscoll A, Kulka J, Bickett-Hickok R, Fellows A, Graham S, Kaleba EO, Hayek SS, Shi X, Sutton NR, Douville N, Mukherjee B, Jamerson K, Brummett CM, Willer CJ
    PLoS One, 2021, 16(2): e0246447 | PMID: 33556117 | PMCID: PMC7870003
    Citations: 3 | AltScore: NA
  109. Trajectories of cognitive function in community-dwelling older adults: A longitudinal study of population heterogeneity.
    Wu Z, Woods RL, Wolfe R, Storey E, Chong TTJ, Shah RC, Orchard SG, McNeil JJ, Murray AM, Ryan J, ASPREE Investigator Group.
    Alzheimers Dement (Amst), 2021, 13(1): e12180 | PMID: 33969173 | PMCID: PMC8088593
    Citations: 3 | AltScore: 13.7
  110. Internet-Based Psychotherapy Intervention for Depression Among Older Adults Receiving Home Care: Qualitative Study of Participants' Experiences.
    Xiang X, Kayser J, Sun Y, Himle J
    JMIR Aging, 2021 Nov 22, 4(4): e27630 | PMID: 34813491 | PMCID: PMC8663658
    Citations: | AltScore: NA
  111. Dual Trajectories of Social Isolation and Dementia in Older Adults: A Population-Based Longitudinal Study.
    Xiang X, Lai PHL, Bao L, Sun Y, Chen J, Dunkle RE, Maust D
    J Aging Health, 2021 Jan, 33(1-2): 63-74 | PMID: 32865104 | PMCID: PMC7855508
    Citations: 1 | AltScore: 7.25
  112. Childhood adversity and major depression in later life: A competing-risks regression analysis.
    Xiang X, Wang X
    Int J Geriatr Psychiatry, 2021 Jan, 36(1): 215-223 | PMID: 32869351
    Citations: 1 | AltScore: NA
  113. The Impact of Late-Life Disability Spectrum on Depressive Symptoms: A Fixed-Effects Analysis of Panel Data.
    Xiang X, Yang Y, Cheng J, An R
    J Gerontol B Psychol Sci Soc Sci, 2021 Mar 14, 76(4): 810-819 | PMID: 32357224 | PMCID: PMC7955956
    Citations: 1 | AltScore: 1
  114. Sestrins regulate muscle stem cell metabolic homeostasis.
    Yang BA, Castor-Macias J, Fraczek P, Cornett A, Brown LA, Kim M, Brooks SV, Lombaert IMA, Lee JH, Aguilar CA
    Stem Cell Reports, 2021 Sep 14, 16(9): 2078-2088 | PMID: 34388363 | PMCID: PMC8452514
    Citations: 2 | AltScore: 8.05
  115. Engineered Tools to Study Intercellular Communication.
    Yang BA, Westerhof TM, Sabin K, Merajver SD, Aguilar CA
    Adv Sci (Weinh), 2021 Feb, 8(3): 2002825 | PMID: 33552865 | PMCID: PMC7856891
    Citations: 6 | AltScore: NA
  116. Cardiac response to adrenergic stress differs by sex and across the lifespan.
    Yusifov A, Chhatre VE, Zumo JM, Cook RF, McNair BD, Schmitt EE, Woulfe KC, Bruns DR
    Geroscience, 2021 Mar 2, 43(4): 1799-1813 | PMID: 33651247 | PMCID: PMC8492879
    Citations: 4 | AltScore: 1
  117. Biopsychosocial pathways in dementia inequalities: Introduction to the Michigan Cognitive Aging Project.
    Zahodne LB
    Am Psychol, 2021 Dec, 76(9): 1470-1481 | PMID: 35266748 | PMCID: PMC9205325
    Citations: | AltScore: 4
  118. Effect of Statin Therapy on Cognitive?Decline and Incident Dementia?in Older Adults.
    Zhou Z, Ryan J, Ernst ME, Zoungas S, Tonkin AM, Woods RL, McNeil JJ, Reid CM, Curtis AJ, Wolfe R, Wrigglesworth J, Shah RC, Storey E, Murray A, Orchard SG, Nelson MR, ASPREE Investigator Group.
    J Am Coll Cardiol, 2021 Jun 29, 77(25): 3145-3156 | PMID: 34167639 | PMCID: PMC8091356
    Citations: 4 | AltScore: 249.5
  119. Commentary: Special care considerations in older adults hospitalized with COVID-19.
    Zietlow KE, Wiggins J, Jenq G, Patel PK, Mody L, Dewar S
    Aging Health Res, 2021 Sep, 1(3): 100023 | PMID: 34151316 | PMCID: PMC8196475
    Citations: 1 | AltScore: NA


Kenneth Schmader
Duke University
Serving since 2017 (5 years)

Alex Smith
San Francisco VA Medical Center
Serving since 2021 (1 years)

Rozalyn Anderson
University of Wisconsin
Serving since 2021 (1 years)

Jenq, Grace (2021)
  • Chairs Award For Impact
Mody, Lona (2021)
  • MICHR Distinguished Clinical and Translational Research Mentor Award


General Brief Description of Minority Activities:

Minority Research:  List activities with minority trainees and research focusing on hypotheses dealing with minority health. Clinical research that has an expected number of minority subjects (a NIH requirement) is NOT what is desired for this section. Only work that has a comparison of minority members to majority members such as work on health disparities should be included. 


Minority Trainee(s):

Emily Briceño-Abreau, PhD, Assistant Professor, Physical Medicine and Rehabilitation, is supported by the REC. Her research focus is on the measurement of cognition across language and education among Mexican American and non-Hispanic white older adults


Jaclynn Hawkins, MSW, PhD, supported by PESC and REC in 2019-2020, was promoted to Associate Professor with Tenure, School of Social Work in 2022. She also was appointed as the new Associate Director of the Vivian A. and James L. Curtis Center for Health Equity Research and Training in 2021. Her research supported by the OAIC focuses on Type 2 diabetes self-management in older African American men.


Trainees Focusing on Minority Health Issues.


Emily Briceño-Abreau, Ph.D.,


Research Articles:


Briceño EM, Mehdipanah R, Gonzales XF, Heeringa SG, Levine DA, Langa KM, Zahs D, Garcia N, Longoria R, Morgenstern LB. Bilingualism, assessment language, and the Montreal Cognitive Assessment in Mexican Americans. J Am Geriatr Soc. 2021 Jul;69(7):1971-1981. doi: 10.1111/jgs.17209. Epub 2021 May 7. PMID: 33963535; PMCID: PMC8273138.

Briceño EM, Mehdipanah R, Gonzales XF, Heeringa SG, Levine DA, Langa KM, Zahs D, Garcia N, Longoria R, Vargas A, Morgenstern LB. Differential Relationships Between the Montreal Cognitive Assessment and Informant-Rated Cognitive Decline Among Mexican Americans and Non-Hispanic Whites. J Geriatr Psychiatry Neurol. 2021 Jul 22:8919887211029383. doi: 10.1177/08919887211029383. Epub ahead of print. PMID: 34291678; PMCID: PMC8782915.

Jones LM, Moss KO, Mitchell J, Still C, Hawkins J, Tang E, Wright KD. Challenges to dietary hypertension self-management as described by a sample of African American older adults. Worldviews Evid Based Nurs. 2022 Feb;19(1):64-72. doi: 10.1111/wvn.12555. Epub 2022 Jan 22. PMID: 35064763.

Leggett AN, Strominger J, Robinson-Lane SG, Maust DT. Disparities in Health Care Task Participation and Provider Communication by Family Caregiver Race J Gen Intern Med. 2022 Apr;37(5):1321-1324. doi: 10.1007/s11606-021-06766-w. Epub 2021 Apr 8. PMID: 33830417; PMCID: PMC8971267.

Tipirneni R, Karmakar M, Maust DT. Trends and Disparities in Functional Impairment among US Adults Age 55-64, 2002 to 2016. J Gen Intern Med. 2021 Dec;36(12):3903-3906. doi: 10.1007/s11606-020-06209-y. Epub 2020 Sep 11. PMID: 32918202; PMCID: PMC8642514.

Minority Trainee(s):
  • Emily Briceño-Abreau, PhD, Assistant Professor, Physical Medicine and Rehabilitation
    Emily Briceño-Abreau, PhD, Assistant Professor, Physical Medicine and Rehabilitation, is supported by the REC. Her research focus is on the measurement of cognition across language and education among Mexican American and non-Hispanic white older adults
  • Jaclynn Hawkins, Ph.D. , Assistant Professor, University of Michigan School of Social Work, Associate Director of the Gender and Health Research Lab’
    REC & PESC Recipient 2020 Type 2 Diabetes Self-Management in Older African American Men: A Peer Leader Pilot Intervention

Minority Grant(s):